2-substituted amino-naphth (1,2-d) imidazol-5-one compounds of pharmaceutically acceptable salts thereof

ABSTRACT

Provided herein are therapeutic and/or prophylactic compounds for mitochondrial or oxidative stress diseases such as cancer, amyotropic lateral sclerosis, Creutzfeldt-Jakob disease, Machado-Joseph disease, spinocerebellar ataxia, Huntington disease, Parkinson disease, Alzheimer disease, myocardial infarction, cerebral infarction, diseases related to aging, diabetes, alcoholic liver injury, chronic obstructive pulmonary disease, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and the like, wherein the compound is represented by formula (1), or reduced forms thereof, or pharmaceutically acceptable salts thereof.

CROSS REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. patent application Ser. No.16/989,582 (filed Aug. 10, 2020), which is a continuation of U.S. patentapplication Ser. No. 16/349,940 (filed May 14, 2019; now U.S. Pat. No.10,738,014), which is a national-phase application under 35 U.S.C. § 371of International Patent Application No. PCT/US2017/061879 (filed Nov.15, 2017), which claims the priority benefit of Japanese Application No.2016-222028 (filed Nov. 15, 2016) and Japanese Application No.2016-250981 (filed Dec. 26, 2016). The entire contents of theseapplications are hereby incorporated by reference herein.

This disclosure relates to 2-substitutedamino-naphth[1,2-d]imidazol-5-one compounds and pharmaceuticallyacceptable salts thereof useful as medicaments, or more particularly, aspharmaceutical compositions comprising a 2-substitutedamino-naphth[1,2-d]imidazol-5-one compound or a pharmaceuticallyacceptable salt thereof. Alternatively, this disclosure is related to atherapeutic agent comprising a 2-substitutedamino-naphth[1,2-d]imidazol-5-one compound or a pharmaceuticallyacceptable salt thereof.

BACKGROUND

Oxidative stress occurs when active oxygen generated by an external orinternal factor overwhelms the processing capacity of a living body.Active oxygen species (e.g., hydrogen peroxide, superoxide radical, andthe like) are produced as a main product or by-product of variousenzymatic reactions in cells. Although the living body is exposed tomany oxidative stresses even under normal conditions, variousantioxidation systems are fully used to maintain the homeostasis of theredox condition. When an excess of active oxygen, peroxides, and thelike, or the collapse of an antioxidation system causes imbalance in theredox condition, the proteins, lipids, and DNAs become disordered andthereby various intra cellular organs become disordered. Accordingly,oxidative stress is believed to be involved in many diseases, such ascancer, lifestyle-related disease, central nervous system disease, lungdisease, heart disease, kidney disease, ischemic disease, diseasesrelated to aging, and the like. Specific examples thereof include,without limitation, amyotrophic lateral sclerosis (ALS), Huntingtondisease, Parkinson disease, Alzheimer disease, Friedreich ataxia (FRDA),Creutzfeldt-Jakob disease, Machado-Joseph disease, spinocerebellarataxia, multiple system atrophy (MS), atherosclerosis, myocardialinfarction, cerebral infarction, senile cognition disorder, diabetes,alcoholic liver injury, non-alcoholic steatohepatitis (NASH), chronicobstructive pulmonary disease (COPD), pulmonary fibrosis, hearing loss,and spinal muscular atrophy (SMA).

Meanwhile, mitochondria are one of the cell organelles in eukaryoticcells, and their main function is to supply ATP (adenosinetriphosphate), which is energy necessary for cells to live. Moreover,since mitochondria are physiologically active oxygen sources undernormal conditions, when an abnormality occurs in a function of themitochondria, it is believed that a supply balance of active oxygen isdisrupted to generate or increase oxidative stress. As described above,there is believed to be a close relationship between the mitochondriaand oxidative stress.

For the above reasons, there is a possibility that various diseasesincluding diseases related to mitochondrial dysfunction, such asmitochondrial disease, neurodegenerative disease, diseases related toaging, and the like, in addition to the above-described diseases, can betreated by suppressing oxidative stress(i.e., returning the balance ofactive oxygen/antioxidation system to normal). In some embodiments,diseases related to mitochondrial dysfunction include diseases such asamyotrophic lateral sclerosis (ALS), Huntington disease, Parkinsondisease, Alzheimer disease, Friedreich ataxia (FRDA), Leber's hereditaryoptic neuropathy (LHON), mitochondrial myopathy, encephalopathy, lacticacidosis, and stroke-like episodes (MELAS), Leigh encephalopathy (LeighSyndrome), Kearns-Sayre syndrome (KSS), chronic progressive externalophthalmoplegia (CPEO), myoclonic epilepsy with ragged-red fibers(Fukuhara disease, MERRF, myoclonic epilepsy, myoclonic epilepsysyndrome), Pearson's disease (pancytopenia, multiple organ dysfunctionsyndrome), and the like. See, e.g., Kevin J. Barnham et al. Nature DrugDiscovery 2004, 3, 205-214; Michael T. Linl et al. Nature 2006, 443,787-795; Bayani Uttara et al. Current Neuropharmacology 2009, 7, 65-74;Toren Finkel et al. Nature 2000, 408, 239-247; Jiang et al.Translational Neurodegeneration 2015, 4, 14-19; Edens B. M., Miller N.,and Ma Y. C. Front. Cell. Neurosci., 2016, 10, 44-59; and D. Simon etal. Journal of Neuroscience 2004, 24(8), 1987-1995.

SUMMARY OF THE INVENTION

The novel compounds represented by the following formula (1) stronglysuppress cell death due to oxidative stress or mitochondrialdysfunction.

[Item 1]

Provided is a compound represented by formula (1):

-   or a reduced form thereof, or a pharmaceutically acceptable salt    thereof, wherein    -   R¹ and R² are each independently-   (1) a hydrogen atom,-   (2) an optionally substituted C₁₋₆alkyl group, an optionally    substituted C₂₋₆alkenyl group, or an optionally substituted    C₂₋₆alkynyl group,-   (3) an optionally substituted C₃₋₁₀alicyclic hydrocarbon group    (wherein the group may contain one or more unsaturated bonds),-   (4) an optionally substituted, 3 to 8-membered heterocyclic group    (wherein the group may contain one or more unsaturated bonds, and a    carbon atom on the ring of the group is bonded with the nitrogen    atom to which R¹ and R² are attached),-   (5) an optionally substituted C₆₋₁₀aryl group, or-   (6) an optionally substituted, 5 to 12-membered monocyclic or    polycyclic heteroaryl group (with the proviso that in the group, a    carbon atom on its ring is bonded with the nitrogen atom to which R¹    and R² are attached), or-   R¹ and R² may be taken together with the nitrogen atom to which they    are attached to form an optionally substituted, 3 to 8-membered,    nitrogen-containing heterocycle (wherein the heterocycle may contain    one or more unsaturated bonds); and    -   R³ is-   (1) an optionally substituted C₆₋₁₀aryl group, or-   (2) an optionally substituted, 5 to 12-membered monocyclic or    polycyclic heteroaryl group (with the proviso that in the group, a    carbon atom on its ring is bonded with the carbon atom to which R³    is attached).

[Item 2]

Provided is the compound according to item 1 or a reduced form thereof,or a pharmaceutically acceptable salt thereof, wherein

-   -   R¹ and R² are each independently

-   (1) a hydrogen atom,

-   (2) a C₁₋₆alkyl group, an optionally substituted C₂₋₆alkenyl group,    or an optionally substituted C₂₋₆alkynyl group (wherein each group    is optionally substituted with one to three substituents    independently selected from the group consisting of a halogen atom,    a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxyl group),

-   (3) a C₃₋₁₀alicyclic hydrocarbon group (wherein the group may    contain one or more unsaturated bonds and the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a C₁₋₆alkyl group, a halogen atom, a    C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxyl group),

-   (4) a 3 to 8-membered saturated heterocyclic group (wherein the    group may contain one or more unsaturated bonds and the group is    optionally substituted with one to four groups independently    selected from the group consisting of

-   (a) a halogen atom,

-   (b) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three halogen atoms),

-   (c) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three halogen atoms), and

-   (d) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups),

-   with the proviso that in the 3 to 8-membered saturated heterocyclic    group, a carbon atom on its ring is bonded with the nitrogen atom to    which R¹ and R² are attached),

-   (5) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to four groups independently selected from the group    consisting of

-   (a) a halogen atom,

-   (b) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three halogen atoms),

-   (c) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three halogen atoms), and

-   (d) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups)), or

-   (6) a 5 to 12-membered monocyclic or polycyclic heteroaryl group    (wherein the group is optionally substituted with one to four groups    independently selected from the group consisting of

-   (a) a halogen atom,

-   (b) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three halogen atoms),

-   (c) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three halogen atoms), and

-   (d) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups),

-   with the proviso that in the 5 to 12-membered monocyclic or    polycyclic heteroaryl group, a carbon atom on its ring is bonded    with the nitrogen atom to which R¹ and R² are attached), or R¹ and    R² may be taken together with the nitrogen atom to which they are    attached to form a 3 to 8-membered, nitrogen-containing heterocycle    (wherein the heterocycle may contain one or more unsaturated bonds    and the heterocycle is optionally substituted with one or two groups    independently selected from the group consisting of a halogen atom,    a C₁₋₆alkyl group, a C₁₋₆alkoxy group, and a hydroxyl group);    -   R³ is

-   (1) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to seven substituents independently selected from the group    consisting of

-   (a) a halogen atom,

-   (b) a hydroxyl group,

-   (c) a cyano group,

-   (d) a C₁₋₆alkylsulfonyl group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a halogen atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),

-   (e) a C₁₋₆alkylaminosulfonyl group (wherein each C₁₋₆alkyl group is    optionally substituted with one to three substituents independently    selected from the group consisting of a halogen atom, a C₁₋₆alkoxy    group, a C₃₋₆cycloalkyl group, and a hydroxyl group),

-   (f) a C₁₋₆alkylcarbonyl group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a halogen atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),

-   (g) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),

-   (h) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),

-   (i) a C₃₋₁₀cycloalkoxy group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a halogen atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),

-   (j) —N(R⁴)COR⁵,

-   (k) —CONR⁶R⁷,

-   (l) —S(O)₂NR⁸R⁹,

-   (m) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and

-   (n) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or

-   two or more substituents on the C₆₋₁₀aryl group may be joined to    form a 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring    (wherein the 9 to 16-membered ring is optionally substituted with    one or two C₁₋₆alkyl groups; or in some embodiments, the 5 to    8-membered non-aromatic carbocyclic or heterocyclic ring is    optionally substituted with one or two C₁₋₆alkyl groups)), or

-   (2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group    (wherein the group is optionally substituted with one to nine    substituents independently selected from the group consisting of

-   (a) a halogen atom,

-   (b) a hydroxyl group,

-   (c) a cyano group,

-   (d) a C₁₋₆alkylsulfonyl group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a halogen atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),

-   (e) a C₁₋₆alkylaminosulfonyl group (wherein each C₁₋₆alkyl group is    optionally substituted with one to three substituents independently    selected from the group consisting of a halogen atom, a C₁₋₆alkoxy    group, a C₃₋₆cycloalkyl group, and a hydroxyl group),

-   (f) a C₁₋₆alkylcarbonyl group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a halogen atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),

-   (g) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),

-   (h) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),

-   (i) a C₃₋₁₀cycloalkoxy group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a halogen atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),

-   (j) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),

-   (k) —N(R¹⁰COR¹¹,

-   (l) —CONR¹²R¹³,

-   (m) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and

-   (n) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or

-   two or more substituents on the 5 to 12-membered monocyclic or    polycyclic heteroaryl group may be joined to form a 5 to 8-membered    non-aromatic carbocyclic or heterocyclic ring (wherein the 8 to    18-membered ring is optionally substituted with one or two C₁₋₆alkyl    groups; or in some embodiments, the 5 to 8-membered non-aromatic    carbocyclic or heterocyclic ring is optionally substituted with one    or two C₁₋₆alkyl groups), with the proviso that in the 5 to    12-membered monocyclic or polycyclic heteroaryl group, a carbon atom    on its ring is bonded with the carbon atom to which R³ is attached);    and

-   R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each    independently a hydrogen atom or a C₁₋₁₀alkyl group optionally    substituted with one to five fluorine atoms, or R⁶ and R⁷, R⁸ and R    9 and R¹² and R¹³ each independently may be taken together to form a    4 to 10-membered, nitrogen-containing heterocycle.

[Item 3]

Provided is the compound according to item 1 or 2 or a reduced formthereof, or a pharmaceutically acceptable salt thereof, wherein R³ is

-   (1) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to seven substituents independently selected from the group    consisting of-   (a) a halogen atom,-   (b) a cyano group,-   (c) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (d) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (e) a C₃₋₁₀cycloalkoxy group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a halogen atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),-   (f) —N(R⁴)COR⁵,-   (g) —CONR⁶R⁷,-   (h) —S(O)₂NR⁸R⁹,-   (i) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (j) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two substituents on the C₆₋₁₀aryl group may be joined to form a 5 to    8-membered non-aromatic carbocyclic or heterocyclic ring (wherein    the 9 to 16-membered ring is optionally substituted with one or two    C₁₋₆alkyl groups; or in some embodiments, the 5 to 8-membered    non-aromatic carbocyclic or heterocyclic ring is optionally    substituted with one or two C₁₋₆alkyl groups)), or-   (2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group    (wherein the group is optionally substituted with one to nine    substituents independently selected from the group consisting of-   (a) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (b) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (c) a C₃₋₁₀cycloalkoxy group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a halogen atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),-   (d) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (e) —N(R¹⁰COR¹¹,-   (f) —CONR¹²R¹³,-   (g) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (h) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two substituents on the 5 to 12-membered monocyclic or polycyclic    heteroaryl group may be joined to form a 5 to 8-membered    non-aromatic carbocyclic or heterocyclic ring (wherein the 8 to    18-membered ring is optionally substituted with one or two C₁₋₆alkyl    groups; or in some embodiments, the 5 to 8-membered non-aromatic    carbocyclic or heterocyclic ring is optionally substituted with one    or two C₁₋₆alkyl groups),-   with the proviso that in the 5 to 12-membered monocyclic or    polycyclic heteroaryl group, a carbon atom on its ring is bonded    with the carbon atom to which R³ is attached); and-   R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each    independently a hydrogen atom or-   a C₁₋₁₀alkyl group optionally substituted with one to five fluorine    atoms, or R⁶ and R⁷, R⁸ and R⁹, and R¹² and R¹³ each independently    may be taken together to form a 4 to 10-membered,    nitrogen-containing heterocycle.

[Item 4]

Provided is the compound according to any one of items 1 to 3 or areduced form thereof, or a pharmaceutically acceptable salt thereof,wherein R³ is

-   (1) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to seven substituents independently selected from the group    consisting of-   (a) a halogen atom,-   (b) a cyano group,-   (c) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom and a C₁₋₆alkoxy group),-   (d) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three halogen atoms),-   (e) —N(R⁴)COR⁵,-   (f) —CONR⁶R⁷,-   (g) —S(O)₂NR⁸R⁹-   (h) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (i) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two substituents on the C₆₋₁₀aryl group may be joined to form a 5 to    8-membered non-aromatic heterocycle (wherein the 5 to 8-membered    non-aromatic heterocycle is optionally substituted with one or two    C₁₋₆alkyl groups)), or-   (2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group    (wherein the group is optionally substituted with one to nine    substituents independently selected from the group consisting of-   (a) a C₁₋₆alkyl group,-   (b) a C₁₋₆alkoxy group,-   (c) a C₃₋₁₀cycloalkoxy group,-   (d) a C₆₋₁₀aryl group,-   (e) —N(R¹⁰)COR¹¹,-   (f) —CONR¹²R¹³,-   (g) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (h) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two substituents on the 5 to 12-membered monocyclic or polycyclic    heteroaryl group may be joined to form a 5 to 8-membered    non-aromatic heterocycle (wherein the 5 to 8-membered non-aromatic    heterocycle is optionally substituted with one or two C₁₋₆alkyl    groups),-   with the proviso that in the 5 to 12-membered monocyclic or    polycyclic heteroaryl group, a carbon atom on its ring is bonded    with the carbon atom to which R³ is attached); and    -   R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each        independently a hydrogen atom or a C₁₋₁₀alkyl group, or R⁶ and        R⁷, R⁸ and R⁹, and R¹² and R¹³ each independently may be taken        together to form a 4 to 10-membered, nitrogen-containing        heterocycle.

[Item 5]

Provided is the compound according to any one of items 1 to 4 or areduced form thereof, or a pharmaceutically acceptable salt thereof,wherein R¹ and R² are each independently

-   (1) a hydrogen atom,-   (2) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group), or-   (3) a C₃₋₁₀alicyclic hydrocarbon group (wherein the group may    contain one or more unsaturated bonds and the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a halogen atom, a C₁₋₆alkyl group, a    C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxyl group), or-   R¹ and R² are taken together with the nitrogen atom to which they    are attached to form a 3 to 8-membered, nitrogen-containing    heterocycle (wherein the heterocycle may contain one or more    unsaturated bonds and the heterocycle is optionally substituted with    one or two groups independently selected from the group consisting    of a halogen atom, a C₁₋₆alkyl group, a C₁₋₆alkoxy group, and a    hydroxyl group).

[Item 6]

-   Provided is the compound according to any one of items 1 to 5 or a    reduced form thereof, or a pharmaceutically acceptable salt thereof,    wherein R¹ and R² are each independently a hydrogen atom, or a    C₁₋₆alkyl group (wherein the group is optionally substituted with    one to three C₁₋₆alkoxy groups), or-   R¹ and R² are taken together with the nitrogen atom to which they    are attached to form a 3 to 8-membered, nitrogen-containing    heterocycle (wherein the heterocycle may contain one or more    unsaturated bonds and the heterocycle is optionally substituted with    one or two groups independently selected from the group consisting    of a C₁₋₆alkyl group, a C₁₋₆alkoxy group, and a hydroxyl group).

[Item 7]

Provided is the compound according to any one of items 1 to 6 or areduced form thereof, or a pharmaceutically acceptable salt thereof,wherein

-   -   R¹ and R² are each independently an optionally substituted        C₁₋₆alkyl group, or    -   R¹ and R² may be taken together with the nitrogen atom to which        they are attached to form an optionally substituted, 3 to        8-membered, nitrogen-containing heterocycle (the heterocycle may        contain one or more unsaturated bonds), and    -   R³ is an optionally substituted C₆₋₁₀aryl group, or

-   an optionally substituted, 5 to 12-membered monocyclic or polycyclic    heteroaryl group (with the proviso that in the group, a carbon atom    on its ring is bonded with the carbon atom to which R³ is attached).

[Item 8]

Provided is the compound according to any one of items 1 to 7 or areduced form thereof, or a pharmaceutically acceptable salt thereof,wherein

-   R¹ and R² are each independently-   a C₁₋₆alkyl group (wherein the group is optionally substituted with    one C₁₋₆alkoxy group), or    -   R¹ and R² may be taken together with the nitrogen atom to which        they are attached to form a 3 to 8-membered, nitrogen-containing        heterocycle (wherein the heterocycle may contain one or more        unsaturated bonds and the heterocycle is optionally substituted        with one C₁₋₆alkyl group);    -   R³ is-   (1) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to seven substituents independently selected from the group    consisting of:-   (a) halogen atom,-   (b) cyano group,-   (c) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom and a C₁₋₆alkoxy group),-   (d) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three halogen atoms),-   (e) —N(R⁴)COR⁵,-   (f) —CONR⁶R⁷,-   (g) —S(O)₂NR⁸R⁹,-   (h) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (i) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two substituents on the C₆₋₁₀aryl group may be joined to form a 5 to    8-membered non-aromatic carbocyclic or heterocyclic ring (wherein    the 9 to 16-membered ring is optionally substituted with one or two    C₁₋₆alkyl groups; or in some embodiments, the 5 to 8-membered    non-aromatic carbocyclic or heterocyclic ring is optionally    substituted with one or two C₁₋₆alkyl groups)), or-   (2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group    (wherein the group is optionally substituted with one to nine    substituents independently selected from the group consisting of-   (a) a C₁₋₆alkyl group,-   (b) a C₁₋₆alkoxy group,-   (c) a C₆₋₁₀aryl group, and-   (d) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups),-   with the proviso that in the 5 to 12-membered monocyclic or    polycyclic heteroaryl group, a carbon atom on its ring is bonded    with the carbon atom to which R³ is attached); and    -   R⁴, R⁵, R⁶, and R⁷ are each independently a hydrogen atom or a        C₁₋₁₀alkyl group, and R⁸ and R⁹ may be taken together to form a        4 to 10-membered, nitrogen-containing heterocycle (wherein the        heterocycle may contain one or more unsaturated bonds).

[Item 9]

Provided is the compound according to any one of items 1 to 8 or areduced form thereof, or a pharmaceutically acceptable salt thereof,wherein R¹ and R² are each independently a hydrogen atom, anunsubstituted C₁₋₆alkyl group, or a C₁₋₆alkyl group substituted with oneto three substituents independently selected from the group consistingof a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and ahydroxyl group; or R¹ and R² may be taken together with the nitrogenatom to which they are attached to form a 3 to 8-membered, saturatednitrogen-containing heterocycle (wherein the heterocycle is optionallysubstituted with one or two groups independently selected from the groupconsisting of a halogen atom, a C₁₋₆alkyl group, a C₁₋₆alkoxy group, anda hydroxyl group).

[Item 10]

Provided is the compound according to any one of items 1 to 9 or areduced form thereof, or a pharmaceutically acceptable salt thereof,wherein R³ is

-   (1) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to four substituents independently selected from the group    consisting of-   (a) a halogen atom,-   (b) a cyano group,-   (c) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (d) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (e) —N(R⁴)COR⁵,-   (f) —CONR⁶R⁷,-   (g) —S(O)₂NR⁸R⁹,-   (h) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (i) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two or more substituents on the C₆₋₁₀aryl group may be joined to    form a 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring    (wherein the 9 to 16-membered ring is optionally substituted with    one or two C₁₋₆alkyl groups; or in some embodiments, the 5 to    8-membered non-aromatic carbocyclic or heterocyclic ring is    optionally substituted with one or two C₁₋₆alkyl groups)), or-   (2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group    (wherein the group is optionally substituted with one to nine    substituents independently selected from the group consisting of-   (a) a halogen atom,-   (b) a cyano group,-   (c) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (d) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (e) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (f) —N(R¹⁰COR¹¹,-   (g) —-CONR¹²R¹³,-   (h) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (i) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two or more substituents on the 5 to 12-membered monocyclic or    polycyclic heteroaryl group may be joined to form a 5 to 8-membered    non-aromatic carbocyclic or heterocyclic ring (wherein the 8 to    18-membered ring is optionally substituted with one or two C₁₋₆alkyl    groups; or in some embodiments, the 5 to 8-membered non-aromatic    carbocyclic or heterocyclic ring is optionally substituted with one    or two C₁₋₆alkyl groups),-   with the proviso that in the 5 to 12-membered monocyclic or    polycyclic heteroaryl group, a carbon atom on its ring is bonded    with the carbon atom to which R³ is attached).

[Item 11]

Provided is the compound according to any one of items 1 to 10 or areduced form thereof, or a pharmaceutically acceptable salt thereof,wherein the compound is selected from the group consisting of thefollowing compounds of formulas

[Item 12]

Provided is the compound according to any one of items 1 to 11 or areduced form thereof, or a pharmaceutically acceptable salt thereof,wherein the compound is selected from the group consisting of thefollowing compounds:

-   2-(dimethylamino)-4-(4-methylphenyl)-5H-naphth[1,2-d]imidazol    -5-one;-   2-(dimethylamino)-4-(2-methylphenyl)-5H-naphth[1,2-d]imidazol    -5-one;-   4-(2-methylphenyl)-2-(4-methylpiperazin-1-yl)-5H-naphth[1,2-d]imidazol-5-one;-   2-(dimethylamino)-4-[2-(morpholin-4-yl)phenyl]-5H-naphth[1,2-d]imidazol-5-one;-   2-(dimethylamino)-4-[2-(trifluoromethyl)phenyl]-5H-naphth[1,2-d]imidazol-5-one;-   2-(dimethylamino)-4-[2-methyl-4-(trifluoromethyl)phenyl]-5H-naphth[1,2-d]imidazol-5-one;-   2-(diethylamino)-4-(2-methyl phenyl)-5H-naphth[1,2-d]imidazol-5-one;-   2-(dimethylamino)-4-[2-methyl-4-(trifluoromethoxy)phenyl]-5H-naphth[1,2-d]imidazol-5-one;-   4-(2-chlorophenyl)-2-(dimethylamino)-5H-naphth[1,2-d]imidazol-5-one    ;-   2-(dimethylamino)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-5H-naphth[1,2-d]imidazol-5-one;-   2-[(2-dimethylamino)-5-oxo-5H-naphth[1,2-d]imidazol-4-yl]benzonitrile;-   4-[(2-dimethylamino)-5-oxo-5H-naphth[1,2-d]imidazol-4-yl]-3-methylbenzonitrile;    and-   2-(dimethylamino)-4-(2-chloro-4-methoxyphenyl)-5H-naphth[1,2-d]imidazol-5-one.

[Item 13]

Provided is a pharmaceutical composition comprising a compound accordingto any one of items 1 to 12 or a reduced form thereof or apharmaceutically acceptable salt thereof.

[Item 14]

Provided is a therapeutic agent and/or a prophylactic agent for adisease caused by or aggravated by oxidative stress or mitochondrialdysfunction, wherein the compound according to any one of items 1 to 12or a reduced form thereof or a pharmaceutically acceptable salt thereofor the pharmaceutical composition according to item 13 is used as anactive ingredient.

[Item 15]

Provided is a method of treating and/or preventing a disease caused byor aggravated by oxidative stress or mitochondrial dysfunction,characterized by administering to a patient in need of the treatmentand/or prevention a therapeutically effective amount of a compoundaccording to any one of items 1 to 12 or a reduced form thereof or apharmaceutically acceptable salt thereof or a therapeutically effectiveamount of a pharmaceutical composition according to item 13.

[Item 16]

Provided is the compound according to any one of items 1 to 12 or areduced form thereof or a pharmaceutically acceptable salt thereof orthe pharmaceutical composition according to item 13 for use in treatingand/or preventing a disease caused by or aggravated by oxidative stressor mitochondrial dysfunction.

[Item 17]

Provided is the therapeutic agent and/or the prophylactic agentaccording to item 14, wherein the disease caused by or aggravated byoxidative stress or mitochondrial dysfunction is amyotrophic lateralsclerosis (ALS), Huntington disease, Parkinson disease, Friedreichataxia (FRDA), Alzheimer disease, Leber's hereditary optic neuropathy(LHON), mitochondrial myopathy, encephalopathy, lactic acidosis, andstroke-like episodes (MELAS), Leigh Syndrome, Kearns-Sayre syndrome(KSS), chronic progressive external ophthalmoplegia (CPEO), myoclonicepilepsy with ragged-red fibers (Fukuhara disease, MERRF, myoclonicepilepsy, myoclonic epilepsy syndrome), or Pearson's disease(pancytopenia, multiple organ dysfunction syndrome).

[Item 18]

Provided is the method of treating and/or preventing according to item15, wherein the disease caused by or aggravated by oxidative stress ormitochondrial dysfunction is amyotrophic lateral sclerosis (ALS),Huntington disease, Parkinson disease, Friedreich ataxia (FRDA),Alzheimer disease, Leber's hereditary optic neuropathy (LHON),mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-likeepisodes (MELAS), Leigh Syndrome, Kearns-Sayre syndrome (KSS), chronicprogressive external ophthalmoplegia (CPEO), myoclonic epilepsy withragged-red fibers (Fukuhara disease, MERRF, myoclonic epilepsy,myoclonic epilepsy syndrome), or Pearson's disease (pancytopenia,multiple organ dysfunction syndrome).

[Item 19]

Provided is the compound according to item 16 or a reduced form thereof,or a pharmaceutically acceptable salt thereof, wherein the diseasecaused by or aggravated by oxidative stress or mitochondrial dysfunctionis amyotrophic lateral sclerosis (ALS), Huntington disease, Parkinsondisease, Friedreich ataxia (FRDA), Alzheimer disease, Leber's hereditaryoptic neuropathy (LHON), mitochondrial myopathy, encephalopathy, lacticacidosis, and stroke-like episodes (MELAS), Leigh Syndrome, Kearns-Sayresyndrome (KSS), chronic progressive external ophthalmoplegia (CPEO),myoclonic epilepsy with ragged-red fibers (Fukuhara disease, MERRF,myoclonic epilepsy, myoclonic epilepsy syndrome), or Pearson's disease(pancytopenia, multiple organ dysfunction syndrome).

In another aspect, provided is the compound according to any one ofitems 1 to 12 or a reduced form thereof or a pharmaceutically acceptablesalt thereof or the pharmaceutical composition of item 13 for themanufacture of a medicament for treating and/or preventing a diseasecaused by or aggravated by oxidative stress or mitochondrialdysfunction.

In the present disclosure, it is intended that one or a plurality of theabove-mentioned aspects, items, embodiments, or characteristics can befurther arbitrarily combined and provided in addition to clearlyexpressed combinations. Still further, embodiments and advantages of thepresent disclosure will be recognized by those skilled in the art fromthe following detailed descriptions.

The compounds of the present disclosure are useful as a noveltherapeutic and/or prophylactic agent for a disease caused by oraggravated by oxidative stress or mitochondrial dysfunction (e.g.,amyotrophic lateral sclerosis, Huntington disease, Parkinson disease,Friedreich ataxia (FRDA), Alzheimer disease, atherosclerosis, myocardialinfarction, cerebral infarction, disease related to aging, diabetes,alcoholic liver injury, chronic obstructive pulmonary disease, Leber'shereditary optic neuropathy (LHON), mitochondrial myopathy,encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), LeighSyndrome, and Kearns-Sayre syndrome (KSS)).

DETAILED DESCRIPTION

The compounds of the present disclosure encompasse, in addition tocompounds of formula (1), compounds of formulae (2) and (3), which arethe reduced forms thereof.

The compounds of the present disclosure may be present in the form of ahydrate and/or a solvate. These hydrates and/or solvates are alsoencompassed by the compounds of the present disclosure.

Since the compounds of formulae (1), (2), and (3) may have one, oroptionally one or more, asymmetric carbon atom(s) and may result ingeometrical isomerism or axial chirality, the compounds may be presentas one or more of several types of stereoisomers. In the presentdisclosure, these individual stereoisomers, and mixtures and racematesthereof are also encompassed by the compounds represented by formulae(1), (2), and (3) of the present disclosure. Further, a deuterated formin which any one or more hydrogen atoms of a compound represented by thegeneral formula (1), (2), or (3) has been converted to or is enriched(beyond naturally-occurring amounts) for a deuterium atom (D) is alsoencompassed by the compound represented by the general formula (1), (2),or (3).

Examples of a “pharmaceutically acceptable salt” of a compoundrepresented by formulae (1), (2), or (3) include salts with an inorganicor organic acid. In some embodiments, salts with an inorganic acidinclude, without limitation, hydrochloride, hydrobromide, nitrate,sulfate, phosphate, and the like. In some embodiments, salts with anorganic acid include, without limitation, formate, acetate,trifluoroacetate, propionate, lactate, tartrate, oxalate, ascorbate,fumarate, maleate, citrate, malonate, methanesulfonate,benzenesulfonate, p-toluenesulfonate, and the like.

The present disclosure also encompasses prodrugs of compounds herein orpharmaceutically acceptable salts thereof. In general, the prodrugs arefunctional derivatives of compounds herein that can be readily convertedto an active compound in vivo.

As used herein, unless otherwise specified, the term “solvate” refers toa compound herein, or a salt thereof, that further comprises an amountof a solvent in a stoichiometric or non-stoichiometric ratio wherein thesolvent is bound by noncovalent intermolecular forces. In the presentdisclosure, one or more types of the solvates can be used incombination. When the solvent is water, the solvate is a hydrate.

In the present specification, the number of substituents of a groupdefined by “optionally substituted” is not particularly limited if thegroup is substitutable, and the substitutents can be one or plural. Inaddition, unless otherwise indicated, the description for each group isalso applied when the group is one part of or a substituent on othergroups. The number of carbon atoms in the definition of “substituent”may be described as, for example, “C₁₋₆” or the like. Specifically, thedescription “C₁₋₆alkyl” is synonymous with an alkyl group having acarbon number from 1 to 6. In addition, in the present specification, asubstituent for which the term “optionally substituted” is not clearlystated refers to an “unsubstituted” substituent.

A “halogen atom” as used herein refers to a fluorine atom, a chlorineatom, a bromine atom, or an iodine atom. Preferably, it is a fluorineatom or a chlorine atom.

An “alkyl group” as used herein refers to a linear or branched,saturated hydrocarbon group. For example, a “C₁₋₄alkyl group,” a“C₁₋₆alkyl group,” or a “C₁₋₁₀alkyl group” refers to an alkyl grouphaving 1 to 4, 1 to 6, or 1 to 10 carbon atoms, respectively. In someembodiments, the “C₁₋₄alkyl group” includes a methyl group, an ethylgroup, a propyl group, an isopropyl group, a butyl group, an isobutylgroup, a sec-butyl group, a tert-butyl group, and the like. An alkylgroup preferably includes a “C₁₋₆alkyl group” and more preferably a“C₁₋₄alkyl group.” In some embodiments, the “C₁₋₆alkyl group” includes,in addition to those described above, a pentyl group, an isopentylgroup, a neopentyl group, a hexyl group, and the like. In someembodiments, the “C₁₋₁₀alkyl group” further includes, in addition tothose described above, a heptyl group, an octyl group, and the like.

An “alkenyl group” as used herein refers to a linear or branched,unsaturated hydrocarbon group that contains at least one double bond.For example, a “C₂₋₆ alkenyl group” refers to a linear or branched,unsaturated hydrocarbon group that has two to six carbon atoms andcontains one to three double bonds. In some embodiments, the “C₂₋₆alkenyl group” includes, for example, a vinyl group, a propenyl group, amethylpropenyl group, a butenyl group, a methylbutenyl group, a pentenylgroup, a hexenyl group, and the like.

An “alkynyl group” as used herein refers to a linear or branched,unsaturated hydrocarbon group that contains at least one triple bond.For example, a “C₂₋₆ alkynyl group” refers to a linear or branched,unsaturated hydrocarbon group that has two to six carbon atoms andcontains one or more triple bonds. In some embodiments, the “C₂₋₆alkynyl group” includes, for example, a propynyl group, a methylpropynylgroup, a butynyl group, a methylbutynyl group, a pentynyl group, ahexynyl group, and the like.

An “alicyclic hydrocarbon group” as used herein refers to a monocyclicor polycyclic hydrocarbon group in which the ring is an aliphatichydrocarbon ring. The ring may contain one or more unsaturated bonds,however, the ring is not aromatic. Examples of the “alicyclichydrocarbon group” include a cycloalkyl group, a cycloalkenyl group, anda cycloalkynyl group. An “alicyclic hydrocarbon group” is optionallysubstituted. In some embodiments, an “alicyclic hydrocarbon group” maybe fused to an aromatic ring (e.g., benzene, naphthalene, pyridine, orthe like). For example, a “C₃₋₁₀alicyclic hydrocarbon group” refers to agroup in which the alicyclic ring portion has 3 to 10 carbon atoms. Insome embodiments, cases where an “alicyclic hydrocarbon group” is fusedto an aromatic ring include groups represented by the following:

and the like. It should be noted that “C₃₋₁₀” indicates the number ofcarbon atoms of an alicyclic hydrocarbon group, and therefore, when itis fused, the total number of carbon atoms contained in such a group maybe 10 or more.

A “cycloalkyl group” as used herein refers to a monocyclic or polycyclicsaturated hydrocarbon group, and also includes fused, bridged, andspirocyclic structures. In some embodiments, a “C₃₋₁₀cycloalkyl group”refers to a cyclic alkyl group having 3 to 10 carbon atoms. For example,the “C₃₋₁₀cycloalkyl group” includes a cyclopropyl group, a cyclobutylgroup, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, acyclooctyl group, an adamantyl group, and the like. Preferably, itincludes a “C₃₋₆cycloalkyl group.”

A “cycloalkenyl group” as used herein refers to a monocyclic orpolycyclic unsaturated hydrocarbon group that contains at least onedouble bond, and also includes fused, bridged, and spirocyclicstructures. In some embodiments, the “C₃₋₁₀cycloalkenyl group” includesa cyclopropenyl group, a methylcyclopropenyl group, a cyclobutenylgroup, a methylcyclobutenyl group, a cyclopentenyl group, a cyclohexenylgroup, and the like.

A “cycloalkynyl group” as used herein refers to a monocyclic orpolycyclic unsaturated hydrocarbon group that contains at least onetriple bond, and also includes fused, bridged, and spirocyclicstructures. In some embodiments, the “cycloalkynyl group” includes acyclooctynyl group and the like.

An “alkoxy group” as used herein refers to a linear or branched,saturated hydrocarbon group that is attached to a main skeleton throughan oxygen atom. For example, a “C₁₋₆alkoxy group” refers to an alkoxygroup having 1 to 6 carbon atoms. In some embodiments, the “C₁₋₆alkoxygroup” includes a methoxy group, an ethoxy group, a propoxy group, a1-methylethoxy group, a butoxy group, a 2-methylpropoxy group, a1-methylpropoxy group, a 1,1-dimethylethoxy group, a pentyloxy group, a3-methylbutoxy group, a 2-methylbutoxy group, a 2,2-dimethylpropoxygroup, a 1-ethylpropoxy group, a 1,1-dimethylpropoxy group, a hexyloxygroup, a 4-methylpentyloxy group, a 3-methylpentyloxy group, a2-methylpentyloxy group, a 1-methylpentyloxy group, a 3,3-dimethylbutoxygroup, a 2,2-dimethylbutoxy group, a 1,1-dimethylbutoxy group, a1,2-dimethylbutoxy group, and the like. It preferably includes a“C₁₋₆alkoxy group” and more preferably a “C₁₋₃alkoxy group.”

A “C₁₋₆ alkylsulfonyl group” as used herein refers to a —S(O)₂R groupwhere R is “C₁₋₆ alkyl” as described for “C₁₋₆ alkyl group” above.Preferably, it includes a “C₁₋₄ alkylsulfonyl group.” In someembodiments, the “C₁₋₆ alkylsulfonyl group” includes, withoutlimitation, a methylsulfonyl group, an ethylsulfonyl group, apropylsulfonyl group, an isopropylsulfonyl group, a butylsulfonyl group,a pentylsulfonyl group, a hexylsulfonyl group, and the like.

A “C₁₋₆ alkylaminosulfonyl group” as used herein refers to a—S(O)₂NR(C₁₋₆ alkyl) group where R is hydrogen or C₁₋₆ alkyl and each“C₁₋₆ alkyl” moiety in “C₁₋₆ alkylaminosulfonyl group” is defined asdescribed in “Ci -6 alkyl group” above. Preferably, it includes a “C₁₋₄alkylaminosulfonyl group.” In some embodiments, the “C₁₋₆alkylaminosulfonyl group” includes, without limitation, mono ordi-C₁₋₆alkylaminosulfonyl groups, such as a methylaminosulfonyl group,an ethylaminosulfonyl group, a propylaminosulfonyl group, adimethylaminosulfonyl group, a diethylaminosulfonyl group, amethylethylaminosulfonyl group, and the like.

A “C₁₋₆alkylcarbonyl group” as used herein refers to a —C(O)R groupwhere R is “C₁₋₆alkyl” as defined in “C₁₋₆alkyl group” above. The“C₁₋₆alkylcarbonyl group” includes, preferably, a “C₁₋₄alkylcarbonylgroup.” In some embodiments, the “C₁₋₆alkylcarbonyl group” includes,without limitation, a methylcarbonyl group, an ethylcarbonyl group, apropylcarbonyl group, a 1-methylethylcarbonyl group, a butylcarbonylgroup, a 2-methylpropylcarbonyl group, a 1-methylpropylcarbonyl group, a1,1-dimethylethylcarbonyl group, and the like.

A “C₃₋₁₀cycloalkoxy group” as used herein refers to an —OR group where Ris “C₃₋₁₀cycloalkyl” as described for “C₃₋₁₀cycloalkyl group” above.Preferably, it includes a “C₃₋₇cycloalkoxy group.” In some embodiments,the “C₃₋₁₀cycloalkoxy group” includes, without limitation, acyclopropoxy group, a cyclobutoxy group, a cyclopentyloxy group, a

cyclohexyloxy group, a cycloheptyloxy group, and the like. A “C₆₋₁₀arylgroup” as used herein refers to an aromatic hydrocarbon group having acarbon number from 6 to 10 carbon atoms. In some embodiments, the“C₆₋₁₀aryl group” includes, without limitation, a phenyl group, a1-naphthyl group, a 2-naphthyl group, and the like.

When the term “optionally substituted C₆₋₁₀aryl group” is used, itincludes, but is not limited to, C₆₋₁₀aryl where two or moresubstituents are joined to form a 5 to 8-membered non-aromaticcarbocyclic or heterocyclic ring (and may be optionally substituted asfurther described herein).

A “5 to 8-membered non-aromatic carbocyclic or heterocyclic ring formedby joining two or more substituents on an aryl group or a heteroarylgroup” as used herein refers to a 5 to 8-membered non-aromaticcarbocyclic or heterocyclic ring having, together with the atoms of anaryl or heteroaryl group, three to six atoms which are independentlyselected from the group consisting of carbon atoms, nitrogen atoms,oxygen atoms, and sulfur atoms. It is preferably a 5 to 7-membered ringand more preferably a 5 or 6-membered ring. All the nitrogen atoms,oxygen atoms, and sulfur atoms described above are ring-constitutingatoms. A 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring,together with the atoms of an aryl or heteroaryl group also encompassesthe case where two non-aromatic rings are fused to an aryl or heteroarylgroup, and further the case where the two non-aromatic rings are fusedto each other. In some embodiments, the “5 to 8-membered non-aromaticcarbocyclic or heterocyclic ring (wherein the ring is optionallysubstituted with one or two C₁₋₆alkyl groups) formed by joining two ormore substituents on an aryl group or a heteroaryl group” includes,without limitation, rings that are fused to an aryl or heteroarylportion of a structure represented by the following:

and the like, or by the following:

and the like.

A “5 to 8-membered non-aromatic heterocycle formed by joining twosubstituents on an aryl group or a heteroaryl group,” as used herein,refers to a 5 to 8-membered non-aromatic heterocycle having, togetherwith the atoms of an aryl or heteroaryl group, three to six atomsindependently selected from the group consisting of carbon atoms,nitrogen atoms, oxygen atoms, and sulfur atoms, with the proviso that atleast one or more of the atoms are heteroatom(s). It is preferably a 5to 7-membered ring and more preferably a 5 or 6-membered ring. All thenitrogen atoms, oxygen atoms, and sulfur atoms described above arering-constituting atoms. In some embodiments, the “5 to 8-memberednon-aromatic heterocycle (wherein the heterocycle is optionallysubstituted with one or two C₁₋₆alkyl groups) formed by joining twosubstituents on an aryl group or a heteroaryl group” includes, withoutlimitation, rings that are fused to an aryl or heteroaryl portion of astructure represented by the following:

and the like.

A “heteroaryl group” as used herein refers to a 5 to 12-memberedmonocyclic or polycyclic heteroaryl group (aromatic). The heteroarylgroup contains one or more (e.g., one to four) heteroatoms independentlyselected from the group consisting of nitrogen atoms, sulfur atoms, andoxygen atoms. It preferably includes a 5 to 10-membered monocyclic orpolycyclic group and more preferably a 5 or 6-membered monocyclicheteroaryl group. In some embodiments, the “heteroaryl group” includes,without limitation, a pyrrolyl group, a thienyl group, a benzothienylgroup, a benzofuranyl group, a benzoxazolyl group, a benzothiazolylgroup, a furyl group, an oxazolyl group, a thiazolyl group, anisoxazolyl group, an isothiazolyl group, a benzisoxazolyl group, abenzisothiazolyl group, an imidazolyl group, a pyrazolyl group, apyridyl group, a pyrazyl group, a pyrimidyl group, a pyridazyl group, aquinolyl group, an isoquinolyl group, a triazolyl group, a triazinylgroup, a tetrazolyl group, an indolyl group, an imidazo[1,2-a]pyridylgroup, a pyrazolo[1,5-a]pyridyl group, a [1,2,4]triazolo[1,5-a]pyridylgroup, a benzimidazolyl group, a quinoxalyl group, a cinnolyl group, aquinazolyl group, an indazolyl group, a naphthyridyl group, aquinolinolyl group, an isoquinolinolyl group, and the like. In someembodiments, the “polycyclic heteroaryl group,” wherein in someembodiments the polycyclic heteroaryl group is optionally substitutedwith a C₁₋₆alkyl groups, includes, without limitation, groups having thepoint of attachment at a position shown below:

and the like. (The points of arrows represent the position of bondingwith the main skeleton.)

A “3 to 8-membered heterocyclic group” as used herein refers to a 3 to8-membered heterocyclic group having one to three heteroatomsindependently selected from the group consisting of nitrogen atoms,oxygen atoms, and sulfur atoms. It is preferably a 4 to 7-membered groupand more preferably 5 or 6-membered group. All the nitrogen atoms,oxygen atoms, and sulfur atoms described above are ring-constitutingatoms. In some embodiments, the “3 to 8-membered heterocyclic group”includes a pyranyl group, a furyl group, a pyrrolidinyl group, animidazolidinyl group, a piperidinyl group, a morpholinyl group, athiomorpholinyl group, a hexamethyleneiminyl group, a thiazolidinylgroup, a tetrahydrofuranyl group, a tetrahydropyridinyl group, anoxetanyl group, a tetrahydropyranyl group, and the like. It should benoted that the “3 to 8-membered heterocyclic group” also encompasses afused, bridged, or spirocyclic heterocyclic groups.

The aforementioned “heterocyclic group” may form a fused ring with a6-membered aromatic hydrocarbon or a 6-membered heteroaryl. For example,the heterocyclic group also encompasses the case where a 5 or 6-memberedheterocyclic group is fused to a 6-membered aromatic hydrocarbon or a6-membered heteroaryl. An example of a 6-membered aromatic hydrocarbon,to which the 5 or 6-membered heterocyclic group is fused, includesbenzo. Examples of 6-membered heteroaryls, to which the 5 or 6-memberedheterocyclic group is fused, include pyridine, pyrimidine, pyridazine,and the like. In some embodiments, a fused heterocyclic group includes adihydroindolyl group, a dihydroisoindolyl group, a dihydropurinyl group,a dihydrobenzodioxinyl group, an indazolyl group, a tetrahydroquinolinylgroup, a tetrahydroisoquinolinyl group, a tetrahydronaphthyridinylgroup, and the like.

A “3 to 8-membered, nitrogen-containing heterocycle” as used hereinrefers to a 3 to 8-membered heterocyclic group having, in addition tothe at least one nitrogen atom, 0 to 2 heteroatoms independentlyselected from the group consisting of nitrogen atoms, oxygen atoms, andsulfur atoms. It is preferably a 4 to 7-membered ring and morepreferably a 5 or 6-membered ring. All the nitrogen atoms, oxygen atoms,and sulfur atoms described above are ring-constituting atoms. In someembodiments, the “3 to 8-membered, nitrogen-containing heterocycle”includes aziridine, azetidine, pyrrolidine, piperidine, piperazine,morpholine, azepane, homopiperazine, azocane, and the like. It should benoted that the “3 to 8-membered, nitrogen-containing heterocycle” groupalso encompasses nitrogen-containing fused, bridged, and spirocyclicheterocyclic groups.

A “4 to 10-membered, nitrogen-containing heterocycle” as used hereinrefers to a 4 to 10-membered heterocyclic group having, in addition toat least one nitrogen atom, 0 to 2 heteroatoms independently selectedfrom the group consisting of nitrogen atoms, oxygen atoms, and sulfuratoms. It is preferably a 4 to 7-membered ring and more preferably a 5or 6-membered ring. All the nitrogen atoms, oxygen atoms, and sulfuratoms described above are ring-constituting atoms. In some embodiments,the “4 to 10-membered, nitrogen-containing heterocycle” includesazetidine, pyrrolidine, piperidine, piperazine, morpholine, azepane,homopiperazine, azocane, octamethylenimine, and the like. It should benoted that the “4 to 10-membered, nitrogen-containing heterocycle” groupalso encompasses nitrogen-containing fused, bridged, and spirocyclicheterocyclic groups.

A “4 to 7-membered cyclic amino group” as used herein refers to asaturated or unsaturated 4 to 7-membered cyclic amino group and mayfurther contain, in addition to at least one nitrogen atom, one or twoheteroatoms, and/or a carbonyl carbon in the ring, where the heteroatomsare independently selected from the group consisting of nitrogen atoms,oxygen atoms, and sulfur atoms. It is preferably a 5 or 6-memberedgroup. In some embodiments, the “4 to 7-membered cyclic amino group”includes an azetidinyl group, a pyrrolidinyl group, a pyrrolyl group, animidazolyl group, a piperidinyl group, a piperazinyl group, amorpholinyl group, an azepanyl group, a homopiperazinyl group, and thelike. It should be noted that the “4 to 7-membered cyclic amino group”also encompasses fused, bridged, and spirocyclic cyclic amino groups.

A compound of the present disclosure represented by formula (1) orformula (2) or (3), which are reduced forms thereof, include R¹, R², R³,R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², and R¹³ and each are as describedbelow. However, the technical scope of the present disclosure is notlimited to the scope of compounds mentioned below.

In some embodiments, R¹ and R² are each independently

-   (1) a hydrogen atom,-   (2) a C₁₋₆alkyl group, an optionally substituted C₂₋₆alkenyl group,    or an optionally substituted C₂₋₆alkynyl group, (wherein each group    is optionally substituted with one to three substituents    independently selected from the group consisting of a fluorine atom,    a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxyl group),-   (3) a C₃₋₁₀alicyclic hydrocarbon group (wherein the group may    contain one or more unsaturated bonds and the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a fluorine atom, a C₁₋₆alkyl group, a    C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxyl group),-   (4) a 3 to 8-membered saturated heterocyclic group (wherein the    group may contain one or more unsaturated bonds and the group is    optionally substituted with one to four groups independently    selected from the group consisting of-   (a) a halogen atom,-   (b) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (c) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three fluorine atoms), and-   (d) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups),-   with the proviso that in the 3 to 8-membered saturated heterocyclic    group, a carbon atom on its ring is bonded with the nitrogen atom to    which R¹ and R² are attached),-   (5) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to four groups independently selected from the group    consisting of-   (a) a halogen atom,-   (b) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (c) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three fluorine atoms), and-   (d) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups)), or-   (6) a 5 to 12-membered monocyclic or polycyclic heteroaryl group    (wherein the group is optionally substituted with one to four groups    independently selected from the group consisting of-   (a) a halogen atom,-   (b) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (c) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three fluorine atoms), and-   (d) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups),-   with the proviso that in the 5 to 12-membered monocyclic or    polycyclic heteroaryl group, a carbon atom on its ring is bonded    with the nitrogen atom to which R¹ and R² are attached); or R¹ and    R² are taken together with the nitrogen atom to which they are    attached to form a 3 to 8-membered, nitrogen-containing heterocycle    (wherein the heterocycle may contain one or more unsaturated bonds    and the heterocycle is optionally substituted with one or two groups    independently selected from the group consisting of a fluorine atom,    a C₁₋₆alkyl group, a C₁₋₆alkoxy group, and a hydroxyl group).

In some embodiments, R¹ and R² are each independently

-   (1) a hydrogen atom,-   (2) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a fluorine atom and a C₁₋₆alkoxy group),-   (3) a C₃₋₁₀alicyclic hydrocarbon group (wherein the group may    contain one or more unsaturated bonds and the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a fluorine atom, a C₁₋₆alkyl group, and    a C₁₋₆alkoxy group),-   (4) a 3 to 8-membered saturated heterocyclic group (wherein the    group may contain one or more unsaturated bonds and the group is    optionally substituted with one to four groups independently    selected from the group consisting of-   (a) a fluorine atom,-   (b) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (c) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three fluorine atoms), and-   (d) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups),-   with the proviso that in the 3 to 8-membered saturated heterocyclic    group, a carbon atom on its ring is bonded with the nitrogen atom to    which R¹ and R² are attached),-   (5) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to four groups independently selected from the group    consisting of-   (a) a fluorine atom,-   (b) a chlorine atom,-   (c) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (d) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three fluorine atoms), and-   (e) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups)), or-   (6) a 5 to 12-membered monocyclic or polycyclic heteroaryl group    (wherein the group is optionally substituted with one to four groups    independently selected from the group consisting of-   (a) a fluorine atom,-   (b) a chlorine atom,-   (c) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (d) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three fluorine atoms), and-   (e) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups),-   with the proviso that in the 5 to 12-membered monocyclic or    polycyclic heteroaryl group, a carbon atom on its ring is bonded    with the nitrogen atom to which R¹ and R² are attached); or R¹ and    R² are taken together with the nitrogen atom to which they are    attached to form a 3 to 8-membered, nitrogen-containing heterocycle    (wherein the heterocycle may contain one or more unsaturated bonds    and the heterocycle is optionally substituted with one or two groups    independently selected from the group consisting of a fluorine atom,    a C₁₋₆alkyl group, a C₁₋₆alkoxy group, and a hydroxyl group).

In some embodiments, R¹ and R² are each independently

-   (1) a hydrogen atom,-   (2) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a fluorine atom and a C₁₋₆alkoxy group),-   (3) a C₃₋₁₀alicyclic hydrocarbon group (wherein the group may    contain one or more unsaturated bonds and the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a fluorine atom and a C₁₋₆alkoxy    group); or-   R¹ and R² are taken together with the nitrogen atom to which they    are attached to form a 3 to 8-membered, nitrogen-containing    heterocycle (wherein the heterocycle may contain one or more    unsaturated bonds and the heterocycle is optionally substituted with    one or two groups independently selected from the group consisting    of a fluorine atom, a C₁₋₆alkyl group, a C₁₋₆alkoxy group, and a    hydroxyl group).

In some embodiments, R¹ and R² are each independently

-   (1) a hydrogen atom,-   (2) a C₁₋₆alkyl group, or-   (3) a C₃₋₁₀alicyclic hydrocarbon group (wherein the group may    contain one or more unsaturated bonds), or-   R¹ and R² are taken together with the nitrogen atom to which they    are attached to form a 3 to 8-membered, nitrogen-containing    heterocycle (wherein the heterocycle may contain one or more    unsaturated bonds).

In some embodiments, R³ is

-   (1) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to seven substituents independently selected from the group    consisting of-   (a) a halogen atom,-   (b) a hydroxyl group,-   (c) a cyano group,-   (d) a C₁₋₆alkylsulfonyl group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a fluorine atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),-   (e) a C₁₋₆alkylaminosulfonyl group (wherein each C₁₋₆alkyl group is    optionally substituted with one to three substituents independently    selected from the group consisting of a fluorine atom, a C₁₋₆alkoxy    group, a C₃₋₆cycloalkyl group, and a hydroxyl group),-   (f) a C₁₋₆alkylcarbonyl group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a fluorine atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),-   (g) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a fluorine atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (h) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a fluorine atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (i) a C₃₋₁₀cycloalkoxy group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a fluorine atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),-   (j) —N(R⁴)COR⁵,-   (k) —CONR⁶R⁷,-   (l) —S(O)₂NR⁸R⁹,

(m) an amino group (wherein the group is optionally substituted with oneor two C₁₋₆alkyl groups), and

-   (n) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two or more substituents on the C₆₋₁₀aryl group may be joined to    form a 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring    (wherein the 9 to 16-membered ring is optionally substituted with    one or two C₁₋₆alkyl groups; or in some embodiments, the 5 to    8-membered non-aromatic carbocyclic or heterocyclic ring is    optionally substituted with one or two C₁₋₆alkyl groups)), or-   (2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group    (wherein the group is optionally substituted with one to nine    substituents independently selected from the group consisting of-   (a) a halogen atom,-   (b) a hydroxyl group,-   (c) a cyano group,-   (d) a C₁₋₆alkylsulfonyl group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a fluorine atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),-   (e) a C₁₋₆alkylaminosulfonyl group (wherein each C₁₋₆alkyl group is    optionally substituted with one to three substituents independently    selected from the group consisting of a fluorine atom, a C₁₋₆alkoxy    group, a C₃₋₆cycloalkyl group, and a hydroxyl group),-   (f) a C₁₋₆alkylcarbonyl group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a fluorine atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),-   (g) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a fluorine atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group) ,-   (h) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a fluorine atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (i) a C₃₋₁₀cycloalkoxy group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a fluorine atom, a C₁₋₆alkoxy group, a    C₃₋₆cycloalkyl group, and a hydroxyl group),-   (j) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a fluorine atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl    group, and a hydroxyl group),-   (k) —N(R¹° COR¹¹,-   (l) —CONR¹²R¹³,-   (m) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (n) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two or more substituents on the 5 to 12-membered monocyclic or    polycyclic heteroaryl group may be joined to form a 5 to 8-membered    non-aromatic carbocyclic or heterocyclic ring (wherein the 8 to    18-membered ring is optionally substituted with one or two C₁₋₆alkyl    groups; or in some embodiments, the 5 to 8-membered non-aromatic    carbocyclic or heterocyclic ring is optionally substituted with one    or two C₁₋₆alkyl groups),-   with the proviso that in the 5 to 12-membered monocyclic or    polycyclic heteroaryl group, a carbon atom on its ring is bonded    with the carbon atom to which R³ is attached); and

R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each independently ahydrogen atom or a C₁₋₁₀alkyl group optionally substituted with one tofive fluorine atoms, or R⁶ and R⁷, R⁸ and R⁹ , and R¹² and R¹³ eachindependently may be taken together to form a 4 to 10-memberednitrogen-containing heterocycle.

In some embodiments, R³ is

-   (1) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to seven substituents independently selected from the group    consisting of-   (a) a fluorine atom,-   (b) a chlorine atom,-   (c) a cyano group,-   (d) a C₁₋₆alkylaminosulfonyl group (wherein each C₁₋₆alkyl group is    optionally substituted with one to three substituents independently    selected from the group consisting of a fluorine atom, a C₁₋₆alkoxy    group, and a hydroxyl group),-   (e) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a fluorine atom, a C₁₋₆alkoxy group, and a hydroxyl    group),-   (f) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a fluorine atom, a C₁₋₆alkoxy group, and a hydroxyl    group),-   (g) a C₃₋₁₀cycloalkoxy group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a fluorine atom, a C₁₋₆alkoxy group,    and a hydroxyl group),-   (h) —N(R⁴)COR⁵,-   (i) —CONR⁶R⁷,-   (j) —S(O)₂NR⁸R⁹,-   (k) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (l) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two substituents on the C₆₋₁₀aryl group may be joined to form a 5 to    8-membered non-aromatic carbocyclic or heterocyclic ring (wherein    the 9 to 16-membered ring is optionally substituted with one or two    C₁₋₆alkyl groups; or in some embodiments, the 5 to 8-membered    non-aromatic carbocyclic or heterocyclic ring is optionally    substituted with one or two C₁₋₆alkyl groups)), or-   (2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group    (wherein the group is optionally substituted with one to nine    substituents independently selected from the group consisting of-   (a) a fluorine atom,-   (b) a chlorine atom,-   (c) a cyano group,-   (d) a C₁₋₆alkylaminosulfonyl group (wherein each C₁₋₆alkyl group is    optionally substituted with one to three substituents independently    selected from the group consisting of a fluorine atom, a C₁₋₆alkoxy    group, and a hydroxyl group),-   (e) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a fluorine atom, a C₁₋₆alkoxy group, and a hydroxyl    group),-   (f) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a fluorine atom, a C₁₋₆alkoxy group, and a hydroxyl    group),-   (g) a C₃₋₁₀cycloalkoxy group (wherein the group is optionally    substituted with one to three substituents independently selected    from the group consisting of a fluorine atom, a C₁₋₆alkoxy group,    and a hydroxyl group),-   (h) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to three substituents independently selected from the group    consisting of a fluorine atom, a C₁₋₆alkoxy group, and a hydroxyl    group),-   (i) —N(R⁸)COR⁹,-   (j) —CONR¹⁰R¹¹,-   (k) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (l) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two substituents on the 5 to 12-membered monocyclic or polycyclic    heteroaryl group may be joined to form a 5 to 8-membered    non-aromatic carbocyclic or heterocyclic ring (wherein the 8 to    18-membered ring is optionally substituted with one or two C₁₋₆alkyl    groups; or in some embodiments, the 5 to 8-membered non-aromatic    carbocyclic or heterocyclic ring is optionally substituted with one    or two C₁₋₆alkyl groups),-   with the proviso that in the 5 to 12-membered monocyclic or    polycyclic heteroaryl group, a carbon atom on its ring is bonded    with the carbon atom to which R³ is attached); and

R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each independently ahydrogen atom or a C₁₋₁₀alkyl group optionally substituted with one tofive fluorine atoms, or R⁶ and R⁷, R⁸ and R 9 and R¹² and R¹³ eachindependently may be taken together to form a 4 to 10-memberednitrogen-containing heterocycle.

In some embodiments, R³ is

-   (1) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to seven substituents independently selected from the group    consisting of-   (a) a fluorine atom,-   (b) a chlorine atom,-   (c) a cyano group,-   (d) a C₁₋₆alkylaminosulfonyl group (wherein each C₁₋₆alkyl group is    optionally substituted with one to three fluorine atoms),-   (e) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (f) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (g) —N(R⁴)COR⁵,-   (h) —CONR⁶R⁷,-   (i) —S(O)₂NR⁸R⁹,-   (j) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (k) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two substituents on the C₆₋₁₀aryl group may be joined to form a 5 to    8-membered non-aromatic carbocyclic or heterocyclic ring (wherein    the 9 to 16-membered ring is optionally substituted with one or two    C₁₋₆alkyl groups; or in some embodiments, the 5 to 8-membered    non-aromatic carbocyclic or heterocyclic ring is optionally    substituted with one or two C₁₋₆alkyl groups)), or-   (2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group    (wherein the group is optionally substituted with one to nine    substituents independently selected from the group consisting of-   (a) a fluorine atom,-   (b) a chlorine atom,-   (c) a cyano group,-   (d) a C₁₋₆alkylaminosulfonyl group (wherein each C₁₋₆alkyl group is    optionally substituted with one to three fluorine atoms),-   (e) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (f) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (g) a C₆₋₁₀aryl group,-   (h) —N(R¹⁰)COR¹¹,-   (i) —CONR¹²R¹³,-   (j) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (k) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two substituents on the 5 to 12-membered monocyclic or polycyclic    heteroaryl group may be joined to form a 5 to 8-membered    non-aromatic carbocyclic or heterocyclic ring (wherein the 8 to    18-membered ring is optionally substituted with one or two C₁₋₆alkyl    groups; or in some embodiments, the 5 to 8-membered non-aromatic    carbocyclic or heterocyclic ring is optionally substituted with one    or two C₁₋₆alkyl groups),-   with the proviso that in the 5 to 12-membered monocyclic or    polycyclic heteroaryl group, a carbon atom on its ring is bonded    with the carbon atom to which R³ is attached); and

R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each independently ahydrogen atom or

-   a C₁₋₁₀alkyl group optionally substituted with one to five fluorine    atoms, or R⁶ and R⁷, R⁸ and R 9 _(and R) ¹² and R¹³ each    independently may be taken together to form a 4 to 10-membered    nitrogen-containing heterocycle.

In some embodiments, R³ is

-   (1) a C₆₋₁₀aryl group (wherein the group is optionally substituted    with one to seven substituents independently selected from the group    consisting of-   (a) a fluorine atom,-   (b) a chlorine atom,-   (c) a cyano group,-   (d) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (e) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (f) —N(R⁴)COR⁵,-   (g) —CONR⁶R⁷,-   (h) —S(O)₂NR⁸R⁹,-   (i) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (j) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two substituents on the C₆₋₁₀aryl group may be joined to form a 5 to    8-membered non-aromatic heterocycle (wherein the 5 to 8-membered    non-aromatic heterocycle is optionally substituted with one or two    C₁₋₆alkyl groups)), or-   (2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group    (wherein the group is optionally substituted with one to nine    substituents independently selected from the group consisting of-   (a) a fluorine atom,-   (b) a chlorine atom,-   (c) a cyano group,-   (d) a C₁₋₆alkyl group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (e) a C₁₋₆alkoxy group (wherein the group is optionally substituted    with one to three fluorine atoms),-   (f) a C₆₋₁₀aryl group,-   (g) —N(R¹⁰)COR¹¹,-   (h) —CONR¹²R¹³,-   (i) an amino group (wherein the group is optionally substituted with    one or two C₁₋₆alkyl groups), and-   (j) a 4 to 7-membered cyclic amino group (wherein the group is    optionally substituted with one or two C₁₋₆alkyl groups), or-   two substituents on the 5 to 12-membered monocyclic or polycyclic    heteroaryl group may be joined to form a 5 to 8-membered    non-aromatic heterocycle (wherein the 5 to 8-membered non-aromatic    heterocycle is optionally substituted with one or two C₁₋₆alkyl    groups),-   with the proviso that in the 5 to 12-membered monocyclic or    polycyclic heteroaryl group, a carbon atom on its ring is bonded    with the carbon atom to which R³ is attached); and

R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each independently ahydrogen atom or a C₁₋₁₀alkyl group optionally substituted with one tofive fluorine atoms, or R⁶ and R⁷, R⁸ and R⁹ , and R¹² and R¹³ eachindependently may be taken together to form a 4 to 10-memberednitrogen-containing heterocycle.

The number of substituent(s) in R¹ and R² includes, without limitation,1 to 4, 1 to 3, 1 to 2, 1, and the like; and, in R³ includes, withoutlimitation, 1 to 9, 1 to 8, 1 to 7, 1 to 6, 1 to 5, 1 to 4, 1 to 3, 1 to2, 1, and the like.

In certain embodiments, methods of producing compounds of the presentdisclosure are illustrated by the following examples. However, the scopeof the present disclosure is certainly not limited thereto. Thefollowing reactions are merely illustrations. The compounds of thepresent disclosure can be produced by appropriately combining known rawmaterial compounds and conventional methods or production methods inaccordance therewith based on knowledge of those skilled in the art ofsynthetic organic chemistry. If a raw material compound to be used iscommercially available, such a commercially available compound also canbe used.

In certain embodiments, a compound represented by formula (1) of thepresent disclosure is produced, for example, by the following productionmethods. It should be noted that a compound used in the followingproduction methods may form a salt thereof as long as it does notinterfere with a reaction.

Production Methods

In certain embodiments, compounds represented by formula (1) or saltsthereof are produced, for example, by methods described below.

In one embodiment, Compound (4), a commercially available product or asubstance produced according to a known synthesis method can be used.Compound (5), a commercially available product or a substance producedaccording to a known synthesis method (for example, InternationalPublication No. 2005/070934 pamphlet) can be used. Compound (7a) andCompound (7b), commercially available products or substances producedaccording to a known synthesis method can be used. It should be notedthat R¹, R², and R³ in Compounds (5), (7a), and (7b) indicate groups asdefined above.

Step 1: Production step of Compound (6)

Compound (6) is produced by treating Compound (4) with Compound (5).Specifically, treating Compound (4) with Compound (5) in the presence ofa base to obtain Compound (6). The base is selected from bases and thelike illustrated below. In one embodiment, the base is potassiumcarbonate. A solvent used in the synthesis of Compound (6) is selectedfrom solvents and the like illustrated below. In one embodiment, thesolvent is acetonitrile. In one embodiment, the temperature of thisreaction is 0 to 150° C. In one embodiment, the time for this reactionis within a range of 0.5 to 24 hours.

Step 2: Production step of Compound (1)

Compound (1) is produced by treating Compound (6) with Compound (7a) or(7b). Specifically, coupling Compound (6) in the presence of a catalystand a base with Compound (7a) or (7b) provides Compound (1). Examples ofthe catalyst include transition metals, such as palladium and the like,salts thereof, complexes thereof, and those provided on a solid support,such as polymers and the like. Bases used in the present step areselected from bases and the like illustrated below. In one embodimentthe base includes potassium carbonate. In another embodiment, the baseincludes sodium carbonate. A solvent used in the present step isselected from solvents and the like illustrated below. In oneembodiment, the solvent includes a mixed solvent of 1,2-dimethoxyethaneand water. In one embodiment, the temperature of the reaction is 0 to150° C. In another embodiment, the time for the reaction is within arange of 0.5 to 24 hours.

Bases used in the above steps 1 and 2 should be appropriately selecteddepending on the types of reactions and raw material compounds, and thelike. Suitable bases include alkali bicarbonates such as sodiumbicarbonate and potassium bicarbonate; alkali carbonates such as sodiumcarbonate and potassium carbonate; metal hydrides such as sodium hydrideand potassium hydride; alkali metal hydroxides such as sodium hydroxideand potassium hydroxide; alkali metal alkoxides such as sodium methoxideand sodium t-butoxide; organic metal bases such as butyl lithium andlithium diisopropylamide; and organic bases such as triethylamine,diisopropylethylamine, pyridine, 4-dimethylaminopyridine (DMAP), and1,8-diazabicyclo[5.4.0]-7-undecene (DBU). Solvents used in the abovesteps 1 and 2 should be appropriately selected depending on the types ofreactions and raw material compounds, and the like. Suitable solventsinclude alcohols such as methanol, ethanol, and isopropanol; ketonessuch as acetone and ethyl methyl ketone; halogenated hydrocarbons suchas methylene chloride and chloroform; ethers such as tetrahydrofuran(THF), dioxane, and 1,2-dimethoxyethane; aromatic hydrocarbons such astoluene and benzene; aliphatic hydrocarbons such as hexane and heptane;esters such as ethyl acetate and propyl acetate; amides such asN,N-dimethylformamide (DMF) and N-methyl-2-pyrrolidone; sulfoxides suchas dimethyl sulfoxide (DMSO); and nitriles such as acetonitrile. Thesesolvents can be used alone or as a mixture of two or more thereof. Inaddition, depending on the type of reaction, organic bases may be usedas solvent.

The compounds of the present disclosure represented by formulae (1),(2), or (3), or an intermediate thereof, can be separated and purifiedby known methods to those skilled in the art. Suitable purificationmethods include extraction, reprecipitation or trituration, columnchromatography (e.g., silica gel column chromatography, ion exchangecolumn chromatography, preparative liquid chromatography, and the like),recrystallization, and the like. The following can be used asrecrystallization solvents: alcohol-based solvents such as methanol,ethanol, 2-propanol, and the like; ether-based solvents such as diethylether and the like; ester-based solvents such as ethyl acetate and thelike; aromatic-hydrocarbon-based solvents such as benzene, toluene, andthe like; ketone-based solvents such as acetone and the like;halogen-based solvents such as dichloromethane, chloroform, and thelike; hydrocarbon-based solvents such as hexane and the like; polaraprotic solvents such as dimethylformamide, acetonitrile, and the like;polar protic solvents such as water; or mixed solvents of two or moreselected from the above solvents. Other purification methods can beused, such as methods described in Jikken Kagaku Koza (The ChemicalSociety of Japan ed., Maruzen), vol. 1, or the like.

In the compounds of the present disclosure represented by formulae (1),(2), or (3), or pharmaceutically acceptable salts thereof, asymmetry mayoccur, or compounds of formulae (1), (2), or (3) may have an asymmetriccarbon or a substituent having an asymmetric carbon. In such compounds,optical isomers, atropisomers, enantiomers, or diastereomers might bepresent. The compounds of the present disclosure also encompass mixturesof these atropisomers, enantiomers, or diastereomers, as well asisolated individual isomers. Compounds with an enantiomeric,diastereomeric, or atropisomeric excess can be produced according to ageneral production method. In some embodiments, asymmetric synthesismight employ starting materials having asymmetry (e.g., menthol, sugars,and amino acids), methods wherein asymmetry is introduced within areaction sequence, methods employing optical resolution, or the like, ata suitable stage of a production step, and the like. Examples of opticalresolution methods include diastereomeric salt formation, wherein thecompound represented by formulae (1), (2), or (3) or intermediatestherefor has a basic functional group, and in nonreactive solvent (e.g.,alcohol-based solvent such as methanol, ethanol, 2-propanol, and thelike; ether-based solvent such as diethyl ether and the like;ester-based solvent such as ethyl acetate and the like;hydrocarbon-based solvent such as aliphatic-hydrocarbon-based solventsuch as hexane and the like; or aromatic-hydrocarbon-based solvent suchas toluene and the like; aprotic solvent such as acetonitrile and thelike; or mixed solvent of two or more selected from the above solvents)using an optically active acid (e.g., a monocarboxylic acid such asmandelic acid, N-benzyloxy-alanine, lactic acid, and the like, adicarboxylic acid such as tartaric acid, o-diisopropylidene tartaricacid, malic acid, and the like, and a sulfonic acid such as camphorsulfonic acid, bromocamphor sulfonic acid, and the like) forms adiastereomeric salt. When an intermediate for the compound of thepresent disclosure represented by formulae (1), (2), or (3) has anacidic functional group such as a carboxylic acid group and the like,optical resolution also can be performed by diastereomeric saltformation using an optically active amine (e.g., organic amines such as1-phenylethylamine, quinine, quinidine, cinchonidine, cinchonine,strychnine, and the like).

In certain embodiments, a temperature to form a diastereomeric salts asdescribed aboce is selected from the range from -50° C. to the boilingpoint of solvent, the range from 0° C. to the boiling point, and therange from room temperature to the boiling point of solvent. In certainembodiments, to improve the optical purity, it may be desirable toincrease a temperature to the vicinity of the boiling point of a solventonce. In certain embodiments thereafter, when a precipitated salt iscollected by filtration, as necessary, the temperature can be cooled toimprove the yield. Regarding the amount of an optically active acid oramine used, in certain embodiments the range from about 0.5 to about 2.0equivalents, and the range of approximately 1 equivalent, relative to asubstrate is suitable. As necessary, recrystallization can be performedin a nonreactive solvent (e.g., alcohol-based solvent such as methanol,ethanol, 2-propanol, and the like; ether-based solvent such as diethylether and the like; ester-based solvent such as ethyl acetate and thelike; hydrocarbon-based solvent such as toluene and the like; aproticsolvent such as acetonitrile and the like; or mixed solvent of two ormore selected from the above solvents) to obtain an optically active orenriched salt in high purity. In addition, in certain embodiments, asalt that is optically resolved as necessary can be treated with an acidor a base by a general method to obtain corresponding free form.

Compounds represented by formula (1) are readily reduced and convertedto a compound represented by formula (2) or (3). For example, in anLC-MS measurement described in the Examples below, when Solution Acontaining formic acid is used as solvent, the existence of a compoundof formula (2) or (3), which is a reduced form of a compound of formula(1), can be confirmed. These reduced form compounds of formulae (2) and(3) are also believed to exhibit an effect to suppress cell death due tooxidative stress, similar to compounds of formula (1). Therefore, thecompounds of the present disclosure encompass, in addition to a compoundof formula (1), compounds of formulae (2) and (3), which are reducedforms thereof.

Among the starting materials and intermediates in respective productionmethods described above, those not amenable to the production methodsdescribed above are commercially available compounds or can besynthesized from a commercially available compound and a known method tothose skilled in the art or a method in accordance therewith.

In certain embodiments, the compounds of the present disclosure andpharmaceutically acceptable salts thereof are useful as noveltherapeutic and/or prophylactic agents for a disease caused by oraggravated by oxidative stress or mitochondrial dysfunction (e.g.,amyotrophic lateral sclerosis (ALS), Huntington disease, Parkinsondisease, Friedreich ataxia (FRDA), Alzheimer disease, multiple systematrophy (MS), Creutzfeldt-Jakob disease, Machado-Joseph disease,spinocerebellar ataxia, atherosclerosis, myocardial infarction, cerebralinfarction, diseases related to aging, diabetes, alcoholic liver injury,non-alcoholic steatohepatitis (NASH), pulmonary fibrosis, hearing loss,spinal muscular atrophy (SMA), chronic obstructive pulmonary disease,Leber's hereditary optic neuropathy (LHON), mitochondrial myopathy,encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), LeighSyndrome and Kearns-Sayre syndrome (KSS), chronic progressive externalophthalmoplegia (CPEO), myoclonic epilepsy with ragged-red fibers(Fukuhara disease, MERRF, myoclonic epilepsy, myoclonic epilepsysyndrome), or Pearson's disease (pancytopenia, multiple organdysfunction syndrome)). In some embodiments, they are useful againstamyotrophic lateral sclerosis (ALS), Huntington disease, Parkinsondisease, and Alzheimer disease (see, e.g., the references cited in theBACKGROUND section herein; G. Nagesh Babu, Neurochemistry International(2008), 52: 1284-1289; Matthias L. Jauslin (2002) Human MolecularGenetics, 11(24): 3055-3063; Luis H. Barbeito (2004) Brain ResearchReviews, 47: 263-274; Sian C. Barber (2006) Biochimica et BiophysicaActa, 1762: 1051-1067). It should be noted that in the presentdisclosure, “prevention (preventing)” or “prophylaxis” is an action toadminister an active ingredient of the present disclosure to a healthyperson that does not show symptoms of a disease, where in certainembodiments the purpose thereof is, for example, to prevent the onset ofa disease. It should be noted that in the present disclosure, “Treatment(treating)” is an action to administer an active ingredient of thepresent disclosure to a person (e.g., a patient) diagnosed as having adisease by a medical doctor.

In certain embodiments, the compounds of the present disclosure andpharmaceutically acceptable salts thereof can be used in combinationwith a brain protection drug (free radical scavenger), such asedaravone, for a purpose of enhancing effects. In addition, compoundsdescribed herein also can be used in combination with a pharmaceuticalagent, such as an anticancer agent, a therapeutic drug for amyotrophiclateral sclerosis, a therapeutic drug for Creutzfeldt-Jakob disease, atherapeutic drug for Machado-Joseph disease, a therapeutic drug forspinocerebellar ataxia, a therapeutic drug for multiple system atrophy(MS), a therapeutic drug for spinal muscular atrophy (SMA), atherapeutic drug for Huntington disease, a therapeutic drug forParkinson disease, a therapeutic drug for Friedreich ataxia (FRDA), atherapeutic drug for Alzheimer disease, a therapeutic drug foratherosclerosis, a therapeutic drug for myocardial infarction, atherapeutic drug for cerebral infarction, a therapeutic drug for senilecognition disorder, a therapeutic drug for disease related to aging, atherapeutic drug for diabetes, a therapeutic drug for alcoholic liverinjury, a therapeutic drug for non-alcoholic steatohepatitis (NASH), atherapeutic drug for chronic obstructive pulmonary disease, atherapeutic drug for pulmonary fibrosis, a therapeutic drug for hearingloss, a therapeutic drug for Leber's hereditary optic neuropathy (LHON),a therapeutic drug for mitochondrial myopathy, encephalopathy, lacticacidosis, and stroke-like episodes (MELAS), a therapeutic drug for LeighSyndrome, a therapeutic drug for Kearns-Sayre syndrome (KSS), atherapeutic drug for chronic progressive external ophthalmoplegia(CPEO), a therapeutic drug for myoclonic epilepsy with ragged-red fibers(Fukuhara disease, MERRF, myoclonic epilepsy, myoclonic epilepsysyndrome), a therapeutic drug for Pearson's disease (pancytopenia,multiple organ dysfunction syndrome), and the like. In addition, for apurpose of suppressing pharmaceutical agent side effects, compoundsdescribed herein can be used in combination with a pharmaceutical agentsuch as an antiemetic, a sleep-inducing drug, an anticonvulsant, avasopressor, an anticoagulant agent, and the like.

The usefulness as a pharmaceutical product of the compounds of thepresent disclosure is verified by a pharmacological test that canconfirm a pharmacological effect, a pharmacokinetic test that canconfirm in vivo kinetics, and a safety test that can confirm safety, orthe like. For example, the pharmaceutical product is verified by testsas described below. These tests can be generally carried out with mice,rats, dogs, monkeys, and the like. In addition, tests can be carried outwhile conscious or under anesthesia as necessary.

These tests are without limitation as long as they can confirmphysiological activity and safety. For example, physiological activityand safety may be verified by the following tests.

Examples of the pharmacological test include a cell death suppressiontest that induces various oxidative stresses using a nerve cell or afibroblast, and the like. Specific examples thereof include, withoutlimitation, a cell viability evaluation test using human dermalfibroblasts derived from Friedreich ataxia patients, a cell viabilityevaluation test using human dermal fibroblasts derived from ALS patientswhere oxidative stress induced cell death is induced with nitric oxide(NO), an ALS animal model test, each of which are described in testexamples, and the like.

Examples of the pharmacokinetic test include, without limitation, ablood concentration evaluation test, a brain transferability evaluationtest, a P-glycoprotein substrate recognition test, a drug interactiontest, a drug metabolism pathway identification test, a dansylglutathione addition test, a cyano addition test, and the like. Examplesof a preferable compound include a compound exhibiting highintracerebral transferability.

Examples of the safety test include a measurement test of blood pressureand heart rate, an electrocardiogram measurement test, general symptomobservations, a general toxicity test, and the like, in addition to invitro tests such as a hERG inhibition test, a cytotoxicity test, theAmes test, and the like.

After a pharmaceutical product compound is taken into a living body, itschemical structure may be changed by undergoing metabolism where ahighly reactive intermediate, i.e., a reactive metabolite may beproduced that expresses toxicity (e.g., hepatotoxicity, allergy,necrosis of tissue, mutagenicity, carcinogenicity, and the like).Certain compounds disclosed herein were tested for stability (CLintintrinsic clearance) in a cyanide trapping assay, and were found to bestable. In general, compounds with higher CLint values may have higherrisks of hepatotoxicity. Since the tested compounds were stable in thecyanide trapping assay, they may be less likely to form protein adductsthat could be hepatotoxic, and thus may have improved safety risk overlonger periods

The compounds of the present invention can be directly administered orformulated using a suitable dosage form for oral administration orparenteral administration. Examples of the dosage form include, but arenot limited to, a tablet, a capsule, powder, granules, a solution, asuspension, an injection, a patch, a poultice, and the like. Aformulation is produced by a known method using a pharmaceuticallyacceptable additive.

The following can be used as an additive, including pharmaceutiallyacceptable additives, such as, without limitation, an excipient,disintegrator, binder, fluidizer, lubricant, coating agent, solvent,solubilizing agent, thickener, dispersing agent, stabilizing agent,sweetener, flavoring agent, and the like. In certain embodiments,pharmaceutically acceptable additives include lactose, mannitol,crystalline cellulose, hydroxypropyl cellulose having low substitutiondegree, corn starch, partially pregelatinized starch, carmellosecalcium, croscarmellose sodium, hydroxypropyl cellulose,hydroxypropylmethyl cellulose, polyvinyl alcohol, magnesium stearate,sodium stearyl fumarate, polyethylene glycol, propylene glycol, titaniumoxide, talc, and the like.

In some embodiments is the use of a compound of the present disclosureor a reduced form thereof or a pharmaceutically acceptable salt thereofor the use of a pharmaceutical composition of the present disclosure forthe manufacture of a medicament for treating and/or preventing a diseasecaused by or aggravated by oxidative stress or mitochondrialdysfunction.

Suitable administration routes for the compounds of the presentdisclosure include, without limitation, oral, parenteral, topical,ocular, or rectal administration. In certain embodiments, the daily dosethereof varies according to the type of compound, administration method,the condition/age of a patient, and the like. For example, in the caseof oral administration, in certain embodiments, about 0.01 to 1000 mg,or about 0.1 to 500 mg, can be administered per kg of body weight of ahuman or mammal ranging from one to several times. In the case ofparenteral administration such as intravenous injection and the like, incertain embodiments, for example, about 0.01 mg to 300 mg, or about 1 mgto 100 mg can be administered per kg of body weight of a human ormammal.

The period of administration of the compound of the present disclosurein combination with a pharmaceutical agent is not limited, and these maybe administered to a subject concurrently or at intervals. In addition,mixtures of the compound of the present disclosure in combination with apharmaceutical agent may be made. The dosage of a combinationpharmaceutical agent can be appropriately selected using clinicallyappropriate dosages. In addition, the mixing ratio of the compound ofthe present disclosure and a combination pharmaceutical agent can beappropriately selected depending on a subject to be administered, anadministration route, target disease, symptoms, combinations, and thelike. For example, in one embodiments, when a subject to be administeredis a human, 0.1 to 1000 parts by weight of a combination pharmaceuticalagent may be used relative to one part by weight of the compound of thepresent disclosure.

EXAMPLES

Hereinafter, the compounds of the disclosure are more specificallydescribed with reference examples, Examples, and test examples. However,the scope of the present disclosure is certainly not limited to theseexamples. It should be noted that compound names shown in the followingreference examples and Examples do not always follow the IUPACnomenclature.

The following abbreviations are sometimes used throughout the presentspecification to simplify a description.

-   Me: methyl-   tert: tertiary-   Boc: tert-butoxycarbonyl-   s: singlet-   brs: broad singlet-   d: doublet-   t: triplet-   q: quartet-   dd: doubled doublet-   m: multiplet-   J: coupling constant-   Hz: Hertz-   THF: tetrahydrofuran-   TFA: trifluoroacetic acid-   CDCl₃: deuterated chloroform-   Acetone-d₆: deuterated acetone

For silica gel column chromatography and amino silica gel columnchromatography used in reference examples and Examples, a silica gelcolumn and an amino silica gel column produced by Yamazen Corporationwere used. Measurement by LC-MS was carried out using various conditionsshown below in Table 1. A retention time (R.T.) represents a time when amass spectrum peak appeared in LC-MS measurements.

TABLE 1 Analysis condition Analyzer Waters ACQUITY UPLC (Registeredtrademark) equipment Column ACQUITY UPLC (Registered trademark) BEH C18Column, 130 Å, 1.7 μm, 2.1 mm X 150 mm Solvent Solution A: 0.05% formicacid in H₂O Solution B: acetonitrile Gradient condition 0.0 min to 1.3min; A/B 90:10~1:99 1.3 min to 1.5 min; A/B 1:99 1.5 min to 2.0 min; A/B90:10 Flow rate 0.75 mL/min Wavelength (UV) 220 nm, 254 nm Columntemperature 40° C.

Unless otherwise specified, for raw material compounds, reactionreagents, and solvents, those commercially available were used.

Reference Example 14-Chloro-2-(dimethylamino)-5H-naphth[1,2-d]imidazol-5-one

2,3-Dichloro-1,4-naphthoquinone (50 g), 1,1-dimethylguanidine sulfatesalt (30 g), and potassium carbonate (46 g) were dissolved inacetonitrile (500 mL) and then the reaction mixture was heated at refluxfor 4 hours. The reaction solution was cooled to room temperature, andthen chloroform was added thereto and the reaction solution wasfiltered. The resulting filtrate was concentrated under reducedpressure, and then chloroform and water were added to the residue andthe target substance was extracted into the organic layer. The resultingorganic layer was washed with saturated brine and then dried overanhydrous sodium sulfate. The organic layer was then concentrated underreduced pressure. Ethyl acetate was added to the residue and the targetsubstance was recrystallized to yield Reference example 1 (32 g). ¹H-NMR(CDCl₃) δ: 8.12 (1H, dd, J=7.3, 1.8 Hz), 8.05 (1H, dd, J=7.6, 1.6 Hz),7.64-7.55 (2H, m), 3.60 (3H, s), 3.50 (3H, s).

-   LC-MS: R.T. 0.82, 260.6 (M+1)

Reference Examples 2 to 6

According to a similar method to Reference example 1, compounds ofReference examples 2 to 6 shown in the following table were obtainedusing corresponding raw materials.

TABLE 2

Reference example R NMR, LCMS 2

¹H-NMR (CDCl₃) δ: 8.13- 8.10 (1H, m), 8.06-8.04 (1H, m), 7.63-7.54 (2H,m), 3.99 (2H, q, J = 7.3 Hz), 3.91 (2H, q, J = 7.3 Hz), 1.40 (3H, t, J =7.3 Hz), 1.37 (3H, t, J = 7.3 Hz). R.T. 1.04 min, m/z 288 (M + 1). 3

¹H-NMR (CDCl₃) δ: 8.13- 8.10 (1H, m), 8.05-8.03 (1H, m), 7.63-7.54 (2H,m), 4.10-4.07 (2H, m), 3.96-3.94 (2H, m), 2.14- 2.06 (4H, m). R.T. 0.86min, m/z 286 (M + 1) 4

¹H-NMR (CDCl₃) δ: 8.13 (1H, dd, J = 7.3, 1.8 Hz), 8.03 (1H, dd, J = 7.3,1.4 Hz), 7.65-7.57 (2H, m), 4.22 (2H, t, J = 4.8 Hz), 4.11 (2H, t, J =4.8 Hz), 3.891-3.87 (4H, m). R.T. 0.84 min, m/z 302 (M + 1). 5

¹H-NMR (CDCl₃) δ: 8.12 (1H, dd, J = 7.8, 1.4 Hz), 8.03 (1H, dd, J = 7.3,1.8 Hz), 7.64-7.56 (2H, m), 4.23 (2H, t, J = 5.0 Hz), 4.12 (2H, t, J =5.0 Hz), 2.63-2.59 (4H, m), 2.38 (3H, s). R.T. 0.51 min, m/z 315 (M + 1)6

¹H-NMR (CDCl₃) δ: 8.14- 8.09 (1.55H, m), 8.06-8.01 (1.55H, m), 7.64-7.54(3.1H, m), 4.13 (2H, t, J = 5.3 Hz), 4.04 (1.1H, t, J = 5.0 Hz), 3.79(1.1H, t, J = 5.0 Hz), 3.70 (2H, t, J = 5.3 Hz), 3.67 (1.65H, s), 3.55(3H, s), 3.39 (1.65H, s), 3.38 (3H, s). R.T. 0.88 min, m/z 305 (M + 1)

The points of the arrows represent the position of bonding with the mainskeleton.

Example 12-(Dimethylamino)-4-(4-methoxyphenyl)-5H-naphth[1,2-d]imidazol-5-one

4-Chloro-2-(dimethylamino)-5H-naphth[1,2-d]imidazol-5-one (2.0 g),4-methoxyphenylboronic acid (1.7 g), potassium carbonate (3.1 g), andtetrakis(triphenylphosphine)palladium (0) (444 mg) were added to a mixedsolution of 1,2-dimethoxyethane (200 mL) and water (40 mL), and thereaction mixture was heated at reflux for 3 hours. The reaction solutionwas cooled to room temperature and then filtered through Celite. Theresulting filtrate was then concentrated under reduced pressure.Chloroform and water were added to the resulting residue, and then thetarget substance was extracted into the organic layer. The resultingorganic layer was washed with saturated brine, and then dried overanhydrous sodium sulfate and concentrated under reduced pressure. Theresidue was purified by silica gel column chromatography and theresulting solid was washed with methanol to yield the compound ofExample 1 (2.1 g). ¹H-NMR (CDCl₃) δ: 8.11 (1H, dd, J=7.3, 1.4 Hz), 8.04(1H, dd, J=7.1, 1.6 Hz), 7.89 (2H, d, J=9.2 Hz), 7.58-7.56 (2H, m), 6.97(2H, d, J=9.2 Hz), 3.85 (3H, s), 3.56 (3H, s), 3.43 (3H, s).

-   LC-MS: R.T. 0.98, 332.6 (M+1)

Examples 2 to 70

In accordance with the method described in Example 1, compounds ofExamples 2 to 70 shown in the following table were obtained using thecompounds of Reference examples 1 to 6 and corresponding raw materials.

TABLE 3

Example R R′ NMR, LCMS 2

¹H-NMR (CDCl₃) δ: 8.13-8.11 (1H, m), 8.06-8.04 (1H, m), 7.74 (2H, d, J =8.3 Hz), 7.62-7.54 (2H, m), 7.24 (2H, d, J = 7.8 Hz), 3.56 (3H, s), 3.42(3H, s), 2.38 (3H, s). R.T. 1.04 min, m/z 316 (M + 1) 3

¹H-NMR (CDCl₃) δ: 8.78 (1H, d, J = 2.3 Hz), 8.14-8.09 (2H, m), 8.03 (1H,dd, J = 8.7, 2.3 Hz), 7.60-7.53 (2H, m), 6.79 (1H, d, J = 8.7 Hz), 3.97(3H, s), 3.55 (3H, s), 3.41 (3H, s). R.T. 0.95 min, m/z 333 (M + 1) 4

¹H-NMR (CDCl₃) δ: 8.10-8.08 (2H, m), 7.63-7.56 (2H, m), 7.30-7.21 (4H,m), 3.55 (3H, s), 3.34 (3H, s), 2.23 (3H, s). R.T. 1.09 min, m/z 316(M + 1) 5

¹H-NMR (CDCl₃) δ: 8.15-8.08 (2H, m), 7.64-7.56 (2H, m), 7.52-7.48 (1H,m), 7.38-7.33 (1H, m), 7.20 (1H, t, J = 7.6 Hz), 7.14 (1H, t, J = 9.2Hz), 3.57 (3H, s), 3.39 (3H, s). R.T. 0.98 min, m/z 320 (M + 1) 6

¹H-NMR (CDCl₃) δ: 8.13-8.10 (1H, m), 8.06-8.03 (1H, m), 7.74 (2H, d, J =7.8 Hz), 7.61-7.52 (2H, m), 7.23 (2H, d, J = 7.8 Hz), 4.05 (2H, t, J =6.9 Hz), 3.86 (2H, t, J = 7.1 Hz), 2.38 (3H, s), 2.08-2.04 (4H, m). R.T.1.04 min, m/z 342 (M + 1) 7

¹H-NMR (CDCl₃) δ: 8.13-8.11 (1H, m), 8.05-8.02 (1H, m), 7.73 (2H, d, J =8.3 Hz), 7.63-7.54 (2H, m), 7.24 (2H, d, J = 7.8 Hz), 4.23-4.18 (2H, m),4.07-4.02 (2H, m), 2.61-2.54 (4H, m), 2.38 (3H, s), 2.37 (3H, s). R.T.0.87 min, m/z 371 (M + 1) 8

¹H-NMR (CDCl₃) δ: 8.14-8.10 (1H, m), 8.09-8.05 (1H, m), 7.63-7.54 (2H,m), 7.45 (1H, t, J = 8.3 Hz), 6.77 (1H, dd, J = 8.5, 2.5 Hz), 6.70 (1H,dd, J = 11.7, 2.5 Hz), 3.83 (3H, s), 3.57 (3H, s), 3.40 (3H, s). R.T.0.97 min, m/z 350 (M + 1) 9

¹H-NMR (CDCl₃) δ: 8.13-8.09 (1H, m), 8.09-8.06 (1H, m), 7.65-7.56 (2H,m), 7.29-7.21 (4H, m), 4.20 (2H, t, J = 5.0 Hz), 3.96 (2H, t, J = 5.0Hz), 2.58 (2H, t, J = 5.3 Hz), 2.51 (2H, t, J = 5.0 Hz), 2.35 (3H, s),2.23 (3H, s). R.T. 0.91 min, m/z 371 (M + 1) 10

¹H-NMR (CDCl₃) δ: 8.12-8.06 (2H, m), 7.62-7.53 (2H, m), 7.39-7.32 (2H,m), 7.05-6.96 (2H, m), 3.77 (3H, s), 3.54 (3H, s), 3.35 (3H, s). R.T.0.81 min, m/z 332 (M + 1) 11

¹H-NMR (CDCl₃) δ: 8.11-8.07 (2H, m), 7.65-7.55 (2H, m), 7.41-7.34 (2H,m), 7.19-7.14 (2H, m), 3.55 (3H, s), 3.50 (4H, t, J = 4.4 Hz), 3.34 (3H,s), 2.96-2.91 (2H, m), 2.84-2.79 (2H, m). R.T. 0.79 min, m/z 387 (M + 1)12

¹H-NMR (CDCl₃) δ: 8.14-8.07 (2H, m), 7.65-7.54 (2H, m), 7.37-7.28 (1H,m), 6.82-6.76 (2H, m), 3.78 (3H, s), 3.56 (3H, s), 3.38 (3H, s). R.T.0.89 min, m/z 350 (M + 1) 13

¹H-NMR (CDCl₃) δ: 8.11-8.03 (2H, m), 7.60-7.54 (2H, m), 7.25-7.16 (2H,m), 6.82-6.73 (2H, m), 3.55 (3H, s), 3.35 (3H, s), 3.31-3.23 (2H, m),3.16-3.09 (2H, m), 1.85-1.70 (4H, m). R.T. 0.75 min, m/z 371 (M + 1) 14

¹H-NMR (CDCl₃) δ: 8.84 (1H, dd, J = 4.1, 1.8 Hz), 8.16 (1H, dd, J = 8.3,1.4 Hz), 8.13-8.10 (2H, m), 7.87 (1H, dd, J = 8.0, 1.6 Hz), 7.81 (1H,dd, J = 7.3, 1.6 Hz), 7.64-7.58 (3H, m), 7.36 (1H, dd, J = 8.3, 4.6 Hz),3.55 (3H, s), 3.29 (3H, s). R.T. 0.67 min, m/z 353 (M + 1) 15

¹H-NMR (CDCl₃) δ: 8.14-8.11 (1H, m), 8.08-8.04 (1H, m), 7.63-7.54 (4H,m), 7.31 (1H, t, J = 8.0 Hz), 7.15 (1H, d, J = 8.3 Hz), 3.57 (3H, s),3.42 (3H, s), 2.40 (3H, s). R.T. 1.08 min, m/z 316 (M + 1) 16

¹H-NMR (CDCl₃) δ: 8.12-8.05 (2H, m), 7.63-7.54 (2H, m), 7.21 (1H, d, J =8.3 Hz), 6.84-6.77 (2H, m), 3.83 (3H, s), 3.55 (3H, s), 3.35 (3H, s),2.22 (3H, s). R.T. 0.94 min, m/z 346 (M + 1) 17

¹H-NMR (CDCl₃) δ: 8.08 (2H, tt, J = 6.6, 2.4 Hz), 7.61-7.54 (2H, m),7.34-7.29 (1H, m), 7.26-7.25 (1H, m), 7.12-7.10 (1H, m), 7.03-7.01 (1H,m), 3.54 (3H, s), 3.33 (3H, s), 2.65 (6H, s). R.T. 0.62 min, m/z 345(M + 1) 18

¹H-NMR (CDCl₃) δ: 8.12-8.11 (1H, m), 8.08-8.06 (1H, m), 7.62-7.60 (2H,m), 7.29-7.23 (4H, m), 4.19-4.18 (2H, m), 3.95-3.94 (2H, m), 3.85 (2H,t, J = 4.6 Hz), 3.79 (2H, t, J = 5.0 Hz), 2.22 (3H, s). R.T. 0.69 min,m/z 358 (M + 1) 19

¹H-NMR (CDCl₃) δ: 8.12-8.07 (2H, m), 7.75 (1H, d, J = 7.8 Hz), 7.63-7.58(3H, m), 7.50 (1H, t, J = 7.6 Hz), 7.36 (1H, d, J = 7.3 Hz), 4.26-4.25(1H, m), 4.16-4.12 (1H, m), 4.00-3.96 (1H, m), 3.92-3.87 (1H, m),2.63-2.45 (4H, m), 2.35 (3H, s). R.T. 0.72 min, m/z 425 (M + 1) 20

¹H-NMR (CDCl₃) δ: 8.11-8.10 (2H, m), 7.75 (1H, d, J = 7.3 Hz), 7.65-7.57(3H, m), 7.50 (1H, t, J = 7.6 Hz), 7.36 (1H, d, J = 7.8 Hz), 3.56 (3H,s), 3.32 (3H, s). R.T. 1.01 min, m/z 370 (M + 1) 21

¹H-NMR (CDCl₃) δ: 8.12-8.08 (2H, m), 7.62-7.58 (2H, m), 7.23 (1H, dd, J= 8.5, 6.2 Hz), 6.97-6.94 (2H, m), 3.57 (3H, s), 3.36 (3H, s), 2.22 (3H,s). R.T. 1.00 min, m/z 334 (M + 1) 22

¹H-NMR (CDCl₃) δ: 8.13-8.05 (2H, m), 7.65-7.56 (2H, m), 7.23 (1H, dd, J= 8.7, 6.0 Hz), 7.00-6.90 (2H, m), 4.23-4.18 (2H, m), 3.99-3.94 (2H, m),2.58 (2H, t, J = 5.0 Hz), 2.53 (2H, t, J = 5.0 Hz), 2.36 (3H, s), 2.22(3H, s). R.T. 0.71 min, m/z 389 (M + 1) 23

¹H-NMR (CDCl₃) δ: 8.14-8.09 (2H, m), 7.67-7.57 (2H, m), 7.52 (1H, s),7.48 (1H, d, J = 8.0 Hz), 7.38 (1H, d, J = 8.0 Hz), 3.58 (3H, s), 3.36(3H, s), 2.28 (3H, s). R.T. 1.22 min, m/z 384 (M + 1) 24

¹H-NMR (CDCl₃) δ: 8.14-8.07 (2H, m), 7.67-7.57 (2H, m), 7.52 (1H, s),7.48 (1H, d, J = 8.3 Hz), 7.37 (1H, d, J = 8.3 Hz), 4.24-4.19 (2H, m),3.99-3.95 (2H, m), 2.61-2.57 (2H, m), 2.56-2.51 (2H, m), 2.36 (3H, s),2.28 (3H, s). R.T. 0.77 min, m/z 439 (M + 1) 25

¹H-NMR (CDCl₃) δ: 8.12-8.08 (2H, m), 7.62-7.57 (2H, m), 7.28-7.23 (4H,m), 4.05-4.01 (1H, m), 3.89-3.83 (2H, m), 3.67-3.63 (1H, m), 2.24 (3H,s), 1.35 (3H, t, J = 7.3 Hz), 1.28 (3H, t, J = 7.1 Hz). R.T. 1.17 min,m/z 344 (M + 1) 26

¹H-NMR (CDCl₃) δ: 8.12-8.09 (2H, m), 7.63-7.58 (2H, m), 7.29 (1H, d, J =8.3 Hz), 7.10-7.08 (2H, m), 3.57 (3H, s), 3.37 (3H, s), 2.24 (3H, s).R.T. 1.23 min, m/z 400 (M + 1) 27

¹H-NMR (CDCl₃) δ: 8.11-8.09 (2H, m), 7.65-7.57 (2H, m), 7.28 (1H, d, J =8.3 Hz), 7.10-7.08 (2H, m), 4.22-4.21 (2H, m), 3.98-3.98 (2H, m), 2.59(2H, t, J = 5.0 Hz), 2.54 (2H, t, J = 5.0 Hz), 2.36 (3H, s), 2.24 (3H,s). R.T. 0.82 min, m/z 455 (M + 1) 28

¹H-NMR (CDCl₃) δ: 8.52 (1H, s), 8.47 (1H, d, J = 5.0 Hz), 8.12-8.11 (2H,m), 7.67-7.59 (2H, m), 7.20 (1H, d, J = 5.0 Hz), 3.59 (3H, s), 3.37 (3H,s), 2.22 (3H, s). R.T. 0.91 min, m/z 317 (M + 1) 29

¹H-NMR (CDCl₃) δ: 8.12-8.07 (2H, m), 7.77-7.72 (1H, m), 7.65-7.55 (3H,m), 7.52-7.46 (1H, m), 7.35 (1H, dd, J = 17.2, 7.6 Hz), 4.23-4.16(0.57H, m), 4.04-3.97 (0.57H, m), 3.94-3.89 (0.43H, m), 3.78-3.72(0.43H, m), 3.71-3.67 (2H, m), 3.62 (1.3H, s), 3.38 (1.7H, s), 3.37(1.7H, s), 3.32 (1.3H, s). R.T. 1.09 min, m/z 414 (M + 1) 30

¹H-NMR (CDCl₃) δ: 8.10-8.08 (2H, m), 7.60-7.58 (2H, m), 7.26-7.24 (4H,m), 4.17-4.14 (0.57H, m), 4.06-4.04 (0.57H, m), 3.95-3.90 (0.43H, m),3.83-3.78 (0.43H, m), 3.70-3.65 (2H, m), 3.62 (1.29H, s), 3.39 (1.71H,s), 3.38 (1.71H, s), 3.35 (1.29H, s), 2.24 (1.71H, s), 2.23 (1.29H, s).R.T. 1.03 min, m/z 360 (M + 1) 31

¹H-NMR (CDCl₃) δ: 8.11-8.08 (2H, m), 7.63-7.57 (2H, m), 7.29-7.26 (2H,m), 7.11 (1H, dd, J = 8.5, 2.5 Hz), 3.88 (3H, s), 3.55 (3H, s), 3.33(3H, s). R.T. 1.02 min, m/z 400 (M + 1) 32

¹H-NMR (CDCl₃) δ: 8.48 (1H, s), 8.44 (1H, d, J = 5.1 Hz), 8.13-8.10 (2H,m), 7.66-7.58 (2H, m), 7.19 (1H, d, J = 5.1 Hz), 3.58 (3H, s), 3.36 (3H,s), 2.24 (3H, s). R.T. 0.58 min, m/z 317 (M + 1) 33

¹H-NMR (CDCl₃) δ: 8.13-8.09 (2H, m), 7.62-7.59 (2H, m), 7.47-7.46 (1H,m), 7.39-7.37 (1H, m), 7.33-7.31 (2H, m), 3.57 (3H, s), 3.36 (3H, s).R.T. 0.98 min, m/z 336 (M + 1) 34

¹H-NMR (CDCl₃) δ: 8.51-8.50 (1H, m), 8.12-8.11 (2H, m), 7.64-7.61 (3H,m), 7.19 (1H, dd, J = 7.8, 5.0 Hz), 3.59 (3H, s), 3.37 (3H, s), 2.47(3H, s). R.T. 0.56 min, m/z 317 (M + 1) 35

¹H-NMR (CDCl₃) δ: 8.11-8.09 (1H, m), 8.07-8.05 (1H, m), 7.61-7.54 (2H,m), 3.75 (3H, s), 3.56 (3H, s), 3.38 (3H, s), 2.19 (3H, s), 2.17 (3H,s). R.T. 0.69 min, m/z 334 (M + 1) 36

¹H-NMR (CDCl₃) δ: 8.11 (2H, dd, J = 7.6, 1.5 Hz), 7.65-7.61 (2H, m),7.56 (1H, s), 7.52 (1H, d, J = 8.0 Hz), 7.37 (1H, d, J = 8.0 Hz), 3.59(3H, s), 3.37 (3H, s), 2.26 (3H, s). R.T. 1.02 min, m/z 341 (M + 1) 37

¹H-NMR (Acetone-D6) δ: 8.14-8.11 (1H, m), 8.06-8.04 (1H, m), 7.77-7.71(2H, m), 7.49-7.47 (1H, m), 7.41-7.35 (3H, m), 4.22-4.18 (2H, m),3.91-3.87 (2H, m), 2.60-2.57 (2H, m), 2.52-2.49 (2H, m), 2.30 (3H, s).R.T. 0.65 min, m/z 391 (M + 1) 38

¹H-NMR (CDCl₃) δ: 8.68 (1H, s), 8.55 (1H, s), 8.06-8.05 (1H, m),7.99-7.97 (1H, m), 7.56-7.53 (2H, m), 3.96 (3H, s), 3.57 (3H, s), 3.49(3H, s). R.T. 0.92 min, m/z 306 (M + 1) 39

¹H-NMR (CDCl₃) δ: 8.12-8.08 (2H, m), 7.65-7.57 (2H, m), 3.59 (3H, s),3.40 (3H, s), 2.37 (3H, s), 2.24 (3H, s). R.T. 0.91 min, m/z 321 (M + 1)40

¹H-NMR (CDCl₃) δ: 8.11-8.09 (1H, m), 8.04-8.02 (1H, m), 7.92 (2H, d, J =9.0 Hz), 7.59-7.52 (2H, m), 6.95 (2H, d, J = 9.0 Hz), 3.87 (4H, t, J =4.8 Hz), 3.55 (3H, s), 3.43 (3H, s), 3.25 (4H, t, J = 4.9 Hz). R.T. 0.90min, m/z 387 (M + 1) 41

¹H-NMR (CDCl₃) δ: 8.14-8.11 (1H, m), 8.08-8.06 (1H, m), 7.90-7.88 (2H,m), 7.64-7.56 (2H, m), 7.47-7.45 (2H, m), 3.58 (3H, s), 3.42 (3H, s),3.12 (6H, s). R.T. 0.83 min, m/z 373 (M + 1) 42

¹H-NMR (CDCl₃) δ: 8.20-8.18 (1H, m), 8.11-8.10 (1H, m), 7.82 (1H, d, J =8.3 Hz), 7.64-7.60 (2H, m), 7.40-7.38 (2H, m), 7.17-7.13 (1H, m), 4.18(3H, s), 3.59 (3H, s), 3.42 (3H, s). R.T. 0.81 min, m/z 356 (M + 1) 43

¹H-NMR (CDCl₃) δ: 8.12-8.08 (2H, m), 7.64-7.53 (3H, m), 7.41-7.27 (3H,m), 4.50 (1H, d, J = 13.2 Hz), 4.41 (1H, d, J = 13.2 Hz), 3.56 (3H, s),3.33 (3H, s), 3.23 (3H, s). R.T. 0.90 min, m/z 346 (M + 1) 44

¹H-NMR (CDCl₃) δ: 8.10-8.09 (2H, m), 7.61-7.57 (2H, m), 7.15 (1H, d, J =7.6 Hz), 7.08 (2H, d, J = 7.6 Hz), 3.55 (3H, s), 3.35 (3H, s), 2.33 (3H,s), 2.18 (3H, s). R.T. 1.06 min, m/z 330 (M + 1) 45

¹H-NMR (CDCl₃) δ: 8.12-8.08 (2H, m), 7.61-7.58 (2H, m), 7.29-7.23 (4H,m), 4.06-4.05 (2H, m), 3.77-3.76 (2H, m), 2.23 (3H, s), 2.04-2.02 (4H,m). R.T. 0.92 min, m/z 342 (M + 1) 46

¹H-NMR (CDCl₃) δ: 8.11-8.09 (2H, m), 7.64-7.56 (2H, m), 3.99 (2H, q, J =7.2 Hz), 3.79 (2H, q, J = 7.2 Hz), 2.37 (3H, s), 2.25 (3H, s), 1.39-1.32(6H, m). R.T. 1.22 min, m/z 349 (M + 1) 47

¹H-NMR (CDCl₃) δ: 8.12-8.11 (1H, m), 8.07-8.06 (1H, m), 7.64-7.60 (2H,m), 4.21 (2H, t, J = 4.9 Hz), 4.00 (2H, t, J = 4.9 Hz), 3.88-3.84 (4H,m), 2.36 (3H, s), 2.23 (3H, s). R.T. 0.94 min, m/z 363 (M + 1) 48

¹H-NMR (CDCl₃) δ: 8.18 (1H, d, J = 7.3 Hz), 8.11 (1H, d, J = 7.3 Hz),7.86 (1H, d, J = 8.3 Hz), 7.64-7.57 (2H, m), 7.40-7.36 (2H, m),7.16-7.11 (1H, m), 4.18 (3H, s), 4.00 (2H, q, J = 7.3 Hz), 3.82 (2H, q,J = 7.3 Hz), 1.35 (3H, t, J = 7.3 Hz), 1.32 (3H, t, J = 7.3 Hz). R.T.0.97 min, m/z 384 (M + 1) 49

¹H-NMR (CDCl₃) δ: 8.10-8.08 (1H, m), 8.03-8.01 (1H, m), 7.95-7.92 (2H,m), 7.56-7.53 (2H, m), 7.00-6.95 (2H, m), 3.96 (2H, q, J = 7.1 Hz), 3.83(2H, q, J = 7.2 Hz), 3.32 (4H, t, J = 5.0 Hz), 2.57 (4H, t, J = 5.1 Hz),2.36 (3H, s), 1.37-1.32 (6H, m). R.T. 0.71 min, m/z 428 (M + 1) 50

¹H-NMR (CDCl₃) δ: 8.13-8.10 (1H, m), 8.06-8.03 (1H, m), 7.90 (2H, d, J =8.7 Hz), 7.60-7.52 (2H, m), 6.97 (2H, d, J = 8.7 Hz), 3.97 (2H, q, J =7.2 Hz), 3.85-3.81 (5H, m), 1.39-1.33 (6H, m). R.T. 1.25 min, m/z 360(M + 1) 51

¹H-NMR (CDCl₃) δ: 8.20-8.12 (3H, m), 7.84 (2H, t, J = 7.6 Hz), 7.69-7.59(2H, m), 7.30-7.27 (1H, m), 4.04 (2H, q, J = 7.2 Hz), 3.83 (2H, q, J =7.2 Hz), 1.41 (6H, t, J = 7.3 Hz). R.T. 1.10 min, m/z 370 (M + 1) 52

¹H-NMR (CDCl₃) δ: 8.11-8.07 (2H, m), 7.61-7.54 (2H, m), 7.21 (1H, d, J =8.3 Hz), 6.84-6.77 (2H, m), 4.06-3.97 (1H, m), 3.94-3.79 (5H, m),3.72-3.60 (1H, m), 2.23 (3H, s), 1.34 (3H, t, J = 7.1 Hz), 1.29 (3H, t,J = 7.1 Hz). R.T. 1.14 min, m/z 374 (M + 1) 53

¹H-NMR (CDCl₃) δ: 8.08-8.03 (2H, m), 7.57-7.51 (2H, m), 7.17 (1H, d, J =8.3 Hz), 6.80-6.77 (2H, m), 4.02-3.95 (1H, m), 3.90-3.77 (2H, m),3.68-3.60 (1H, m), 3.31 (4H, t, J = 4.6 Hz), 2.65 (4H, brs), 2.40 (3H,s), 2.20 (3H, s), 1.32 (3H, t, J = 7.3 Hz), 1.26 (3H, t, J = 7.3 Hz).R.T. 0.75 min, m/z 442 (M + 1) 54

¹H-NMR (CDCl₃) δ: 8.71 (1H, s), 8.55 (1H, s), 8.07-8.03 (1H, m),8.00-7.97 (1H, m), 7.58-7.48 (2H, m), 4.01-3.94 (5H, m), 3.89 (2H, q, J= 7.2 Hz), 1.41 (3H, t, J = 7.1 Hz), 1.36 (3H, t, J = 7.1 Hz). R.T. 1.16min, m/z 334 (M + 1) 55

¹H-NMR (CDCl₃) δ: 8.69 (1H, s), 8.56 (1H, s), 8.06-8.04 (1H, m),7.99-7.96 (1H, m), 7.57-7.49 (2H, m), 4.05 (2H, t, J = 6.2 Hz), 3.96(3H, s), 3.93 (2H, t, J = 6.4 Hz), 2.13-2.07 (4H, m). R.T. 0.94 min, m/z332 (M + 1) 56

¹H-NMR (CDCl₃) δ: 8.17-8.15 (1H, m), 8.10-8.08 (1H, m), 7.96 (1H, d, J =0.9 Hz), 7.93 (1H, d, J = 0.9 Hz), 7.76-7.73 (1H, m), 7.66-7.57 (3H, m),4.11 (3H, s), 3.59 (3H, s), 3.44 (3H, s). R.T. 0.95 min, m/z 356 (M + 1)57

¹H-NMR (CDCl₃) δ: 8.17-8.14 (1H, m), 8.11-8.07 (1H, m), 7.98 (1H, s),7.97 (1H, s), 7.74 (1H, d, J = 8.5 Hz), 7.67-7.56 (3H, m), 4.10 (3H, s),4.00 (2H, q, J = 7.1 Hz), 3.83 (2H, q, J = 7.1 Hz), 1.38 (3H, t, J = 7.1Hz), 1.37 (3H, t, J = 7.1 Hz). R.T. 1.16 min, m/z 384 (M + 1) 58

¹H-NMR (CDCl₃) δ: 8.32 (1H, t, J = 1.7 Hz), 8.13 (1H, dd, J = 7.4, 1.3Hz), 8.09-8.04 (2H, m), 7.87-7.84 (1H, m), 7.65-7.56 (2H, m), 7.52 (1H,t, J = 7.8 Hz), 6.19 (1H, br s), 5.53 (1H, br s), 4.00 (2H, q, J = 7.2Hz), 3.83 (2H, q, J = 7.2 Hz), 1.373 (3H, t, J = 7.2 Hz), 1.370 (3H, t,J = 7.2 Hz). R.T. 0.91 min, m/z 373 (M + 1) 59

¹H-NMR (CDCl₃) δ: 8.10 (1H, dd, J = 7.3, 1.4 Hz), 8.05 (1H, dd, J = 6.9,1.4 Hz), 7.75-7.72 (2H, m), 7.62-7.54 (3H, m), 7.42-7.34 (2H, m), 3.56(3H, s), 3.44 (3H, s), 2.13 (3H, s). R.T. 0.60 min, m/z 359 (M + 1) 60

¹H-NMR (CDCl₃) δ: 8.89 (1H, d, J = 1.8 Hz), 8.14 (1H, dd, J = 8.7, 1.8Hz), 8.08-8.06 (1H, m), 8.03-8.00 (1H, m), 7.57-7.50 (2H, m), 6.68 (1H,d, J = 9.2 Hz), 3.95 (2H, q, J = 7.3 Hz ), 3.85-3.79 (6H, m), 3.59-3.57(4H, m), 1.33 (3H, t, J = 7.3 Hz), 1.32 (3H, t, J = 7.3 Hz). R.T. 0.96min, m/z 416 (M + 1) 61

¹H-NMR (CDCl₃) δ: 8.88 (1H, d, J = 2.3 Hz), 8.13 (1H, dd, J = 8.7, 2.3Hz), 8.08-8.06 (1H, m), 8.03-8.00 (1H, m), 7.57-7.50 (2H, m), 6.70 (1H,d, J = 9.2 Hz), 3.95 (2H, q, J = 7.3 Hz), 3.82 (2H, q, J = 7.3 Hz), 3.75(4H, brs), 2.64 (4H, brs), 2.43 (3H, s), 1.33 (3H, t, J = 7.3 Hz), 1.32(3H, t, J = 7.3 Hz). R.T. 0.76 min, m/z 429 (M + 1) 62

¹H-NMR (CDCl₃) δ: 8.08-8.03 (2H, m), 7.59-7.52 (2H, m), 7.17 (1H, d, J =8.7 Hz), 6.80-6.77 (2H, m), 3.52 (3H, s), 3.32 (3H, s), 3.27 (4H, t, J =4.6 Hz), 2.59 (4H, t, J = 4.6 Hz), 2.36 (3H, s), 2.18 (3H, s). R.T. 0.63min, m/z 414 (M + 1) 63

¹H-NMR (CDCl₃) δ: 8.09-8.04 (2H, m), 7.60-7.53 (2H, m), 7.17 (1H, d, J =8.3 Hz), 6.79-6.75 (2H, m), 4.04 (2H, q, J = 6.9 Hz), 3.53 (3H, s), 3.33(3H, s), 2.19 (3H, s), 1.40 (3H, t, J = 6.9 Hz). R.T. 1.01 min, m/z 360(M + 1) 64

¹H-NMR (CDCl₃) δ: 8.09-8.03 (2H, m), 7.59-7.50 (2H, m), 7.17 (1H, d, J =8.3 Hz), 6.79-6.75 (2H, m), 4.07-3.96 (3H, m), 3.91-3.78 (2H, m),3.69-3.62 (1H, m), 2.20 (3H, s), 1.40 (3H, t, J = 6.9 Hz), 1.32 (3H, t,J = 6.9 Hz), 1.27 (3H, t, J = 6.9 Hz). R.T. 1.21 min, m/z 388 (M + 1) 65

¹H-NMR (CDCl₃) δ: 8.48 (1H, dd, J = 4.9, 2.0 Hz), 8.11-8.08 (2H, m),7.63-7.55 (3H, m), 7.18 (1H, dd, J = 7.6, 4.9 Hz), 4.08-3.99 (1H, m),3.93-3.78 (2H, m), 3.68-3.59 (1H, m), 2.47 (3H, s), 1.34 (3H, t, J = 7.3Hz), 1.27 (3H, t, J = 7.3 Hz). R.T. 0.70 min, m/z 345 (M + 1) 66

¹H-NMR (CDCl₃) δ: 8.10-8.04 (2H, m), 7.76 (1H, d, J = 7.8 Hz), 7.69 (1H,s), 7.61-7.50 (3H, m), 7.36 (1H, t, J = 7.8 Hz), 3.96 (2H, q, J = 7.1Hz), 3.83 (2H, q, J = 7.1 Hz), 2.10 (3H, s), 1.36-1.30 (6H, m). R.T.0.93 min, m/z 387 (M + 1) 67

¹H-NMR (CDCl₃) δ: 8.10-8.08 (2H, m), 7.68-7.56 (4H, m), 7.42 (1H, d, J =8.0 Hz), 4.01-3.91 (2H, m), 3.76-3.69 (6H, m), 3.06 (4H, t, J = 4.4 Hz),2.30 (3H, s), 1.35 (3H, t, J = 7.1 Hz), 1.27 (3H, t, J = 7.1 Hz). R.T.0.70 min, m/z 493 (M + 1) 68

¹H-NMR (CDCl₃) δ: 8.05-7.98 (2H, m), 7.61-7.32 (6H, m), 3.95-3.90 (2H,m), 3.79-3.77 (2H, m), 3.45 (4H, brs), 1.32-1.26 (6H, m), 1.16 (3H, t, J= 7.1 Hz), 0.93 (3H, t, J = 7.1 Hz). R.T. 1.13 min, m/z 429 (M + 1) 69

¹H-NMR (CDCl₃) δ: 8.14-8.11 (2H, m), 7.97 (1H, d, J = 0.7 Hz), 7.72 (1H,dd, J = 8.0, 1.0 Hz), 7.64-7.58 (2H, m), 7.32-7.30 (1H, m), 7.19-7.15(1H, m), 4.07-3.82 (5H, m), 3.78-3.61 (2H, m), 1.34 (3H, t, J = 7.1 Hz),1.23 (3H, t, J = 7.1 Hz). R.T. 1.08 min, m/z 384 (M + 1) 70

¹H-NMR (CDCl₃) δ: 8.15-8.06 (2H, m), 7.64-7.56 (3H, m), 7.34 (1H, s),7.17 (1H, s), 4.03-3.89 (2H, m), 3.80-3.71 (1H, m), 3.67-3.59 (1H, m),2.26 (3H, s), 1.35 (3H, t, J = 7.3 Hz), 1.19 (3H, t, J = 7.1 Hz). R.T.0.97 min, m/z 384 (M + 1)

The points of the arrows represent the position of bonding with the mainskeleton.

Example 712-[(2-dimethylamino)-5-oxo-5H-naphth[1,2-d]imidazol-4-yl]benzonitrile

4-Chloro-2-(dimethylamino)-5H-naphth[1,2-d]imidazol-5-one (200 mg),2-(2-cyanophenyl)-4,4,5,5,5-tetramethyl-1,3,2-dioxaborolane (353 mg),and bis(tri-tert-butylphosphine)palladium (0) (39 mg) were added to amixed solution of 1,2-dimethoxyethane (12 mL) and aqueous saturatedsodium carbonate solution (2 mL), and the reaction mixture was stirredat 120° C. for 30 minutes under microwave irradiation. The reactionsolution was cooled to room temperature, and then water and chloroformwere added to the reaction solution, and the target substance wasextracted into the organic layer. The resulting organic layer was washedwith saturated brine, and then dried over anhydrous sodium sulfate, andconcentrated under reduced pressure. The residue was purified by silicagel column chromatography, and then the resulting solid was washed withethyl acetate to yield Example 71 (15.5 mg). ¹H-NMR (CDCl₃) δ: 8.17-8.15(1H, m), 8.11-8.09 (1H, m), 7.76-7.74 (1H, m), 7.67-7.58 (4H, m),7.45-7.43 (1H, m), 3.60 (3H, s), 3.41 (3H, s).

-   LC-MS: R.T. 0.93, 327.5 (M+1)

Examples 72 to 81

In accordance with the method described in Example 71, compounds ofExamples 72 to 81 shown in the following table were obtained usingcompounds of Reference examples 1 to 6 and corresponding raw materials.

TABLE 4 Example R R′ NMR, LCMS 72

¹H-NMR (CDCl₃) δ: 8.09-8.08 (1H, m), 8.01-8.00 (1H, m), 7.98-7.94 (2H,m), 7.55-7.52 (2H, m), 6.79-6.75 (2H, m), 3.53 (3H, s), 3.42 (3H, s),3.02 (6H, s). R.T. 0.92 min, m/z 345 (M + 1) 73

¹H-NMR (CDCl₃) δ: 8.11-8.06 (2H, m), 7.64-7.54 (2H, m), 7.40-7.33 (2H m)7.19-7.11 (2H, m), 3.55 (3H, s), 3.34 (3H, s), 2.93-2.86 (2H, m),2.83-2.75 (2H, m), 2.67 (4H, t, J = 4.6 Hz). R.T. 0.55 min, m/z 386(M + 1) 74

1H-NMR (CDCl₃) δ: 8.11-8.08 (1H, m), 8.03-8.01 (1H, m), 7.91 (2H, d, J =9.2 Hz), 7.56-7.54 (2H, m), 6.96 (2H, d, J = 8.7 Hz), 3.55 (3H, s), 3.42(3H, s), 3.31 (4H, t, J = 5.3 Hz), 2.72-2.69 (5H, m), 1.10 (6H, d, J =6.4 Hz). R.T. 0.65 min, m/z 428 (M + 1) 75

¹H-NMR (CDCl₃) δ: 8.09-8.06 (1H, m), 8.04-8.03 (1H, m), 7.73 (1H, s),7.58-7.55 (2H, m), 3.88 (3H, s), 3.56 (3H, s), 3.40 (3H, s), 2.36 (3H,s). R.T. 0.71 min, m/z 320 (M + 1) 76

1H-NMR (CDCl₃) δ: 8.12 (1H, d, J = 7.1 Hz), 8.07-8.05 (2H, m), 7.60-7.46(6H, m), 7.40-7.38 (1H, m), 3.58 (3H, s), 3.44 (3H, s), 2.38 (3H, s).R.T. 1.00 min, m/z 382 (M + 1) 77

¹H-NMR (CDCl₃) δ: 8.11-8.06 (1H, m), 8.03-7.97 (1H, m), 7.58-7.51 (4H,m), 6.71 (1H, d, J = 8.5 Hz), 4.29 (2H, t, J = 4.4 Hz), 3.53 (3H, s),3.43 (3H, s), 3.33 (2H, t, J = 4.5 Hz), 2.95 (3H, s). R.T. 0.89 min, m/z373 (M + 1) 78

¹H-NMR (CDCl₃) δ: 8.14 (1H, dd, J = 7.4, 1.6 Hz), 8.08 (1H, dd, J = 7.3,1.5 Hz), 7.97 (2H, dd, J = 7.8, 1.7 Hz), 7.65-7.57 (2H, m), 7.44-7.42(3H, m), 3.61 (3H, s), 3.45 (3H, s), 2.51 (3H, s). R.T. 1.25 min, m/z399 (M + 1) 79

¹H-NMR (CDCl₃) δ: 8.12-8.10 (1H, m), 8.05-8.04 (1H, m), 7.59-7.56 (3H,m), 7.49 (1H, dd, J = 8.4, 2.1 Hz), 7.00 (1H, d, J = 8.5 Hz), 4.26 (4H,dd, J = 10.7, 5.1 Hz), 3.56 (3H, s), 3.44 (3H, s), 2.24-2.18 (2H, m).R.T. 1.03 min, m/z 374 (M + 1) 80

¹H-NMR (CDCl₃) δ: 8.11-8.08 (1H, m), 8.03-8.01 (1H, m), 7.91 (2H, d, J =9.3 Hz), 7.58-7.52 (2H, m), 6.96 (2H, d, J = 9.3 Hz), 3.54 (3H, s), 3.42(3H, s), 3.31 (4H, t, J = 5.1 Hz), 2.57 (4H, t, J = 5.1 Hz), 2.35 (3H,s). R.T. 0.61 min, m/z 400 (M + 1) 81

¹H-NMR (CDCl₃) δ: 8.12-8.07 (2H, m), 7.75 (1H, d, J = 7.8 Hz), 7.62-7.60(3H, m), 7.51-7.49 (1H, m), 7.35 (1H, d, J = 7.6 Hz), 4.21-4.16 (2H, m),3.94-3.91 (2H, m), 3.85 (2H, t, J = 4.9 Hz), 3.79-3.77 (2H, m). R.T.1.08 min, m/z 412 (M + 1)

The points of the arrows represent the position of bonding with the mainskeleton.

Examples 82 to 96

In accordance with the method described in Example 1, compounds ofExamples 82 to 96 shown in the following table were synthesized usingthe compounds of Reference examples 1 and 2 and corresponding rawmaterials.

TABLE 5 Example R R′ NMR, LCMS 82

¹H-NMR (CDCl₃) δ: 8.11-8.09 (2H, m), 7.62-7.54 (2H, m), 7.29 (1H, d, J =8.7 Hz), 7.07 (1H, d, J = 2.8 Hz), 6.86 (1H, dd, J = 8.7, 2.7 Hz), 3.81(3H, s), 3.54 (3H, s), 3.36 (3H, s). R.T. 1.02 min, m/z 367 (M + 1) 83

¹H-NMR (CDCl₃) δ: 8.13-8.04 (2H, m), 7.64-7.54 (2H, m), 7.15 (1H, d, J =8.3 Hz), 6.84-6.81 (2H, m), 3.77 (3H, s), 3.54 (3H, s), 3.34 (3H, s),2.13 (3H, s). R.T. 0.97 min, m/z 346 (M + 1) 84

¹H-NMR (CDCl₃) δ: 8.11-8.06 (2H, m), 7.61-7.50 (2H, m), 7.29 (1H, d, J =8.7 Hz), 7.01 (1H, d, J = 2.8 Hz), 6.86 (1H, dd, J = 8.7, 2.8 Hz),4.03-3.68 (7H, m), 1.33 (3H, t, J = 7.3 Hz), 1.28 (3H, t, J = 7.3 Hz).R.T. 1.22 min, m/z 395 (M + 1) 85

¹H-NMR (CDCl₃) δ: 8.10-8.07 (2H, m), 7.62-7.54 (2H, m), 7.15 (1H, d, J =8.0 Hz), 6.84-6.80 (2H, m), 4.04-3.70 (7H, m), 2.14 (3H, s), 1.33 (3H,t, J = 7.1 Hz), 1.27 (3H, t, J = 7.1 Hz). R.T. 1.18 min, m/z 374 (M + 1)86

¹H-NMR (CDCl₃) δ: 8.12-8.06 (2H, m), 7.63-7.54 (2H, m), 7.33 (1H, d, J =8.7 Hz), 6.91 (1H. d, J = 2.8 Hz), 6.85 (1H, dd, J = 8.7, 2.8 Hz), 3.78(3H, s), 3.55 (3H, s), 3.35 (3H, s). R.T. 1.04 min, m/z 367 (M + 1) 87

¹H-NMR (CDCl₃) δ: 8.10-8.05 (2H, m), 7.61-7.53 (2H, m), 7.19 (1H, t, J =7.8 Hz), 6.87-6.84 (2H, m), 3.84 (3H, s), 3.53 (3H, s), 3.32 (3H, s),2.05 (3H, s). R.T. 0.98 min, m/z 346 (M + 1) 88

¹H-NMR (CDCl₃) δ: 8.10-8.06 (2H, m), 7.60-7.53 (2H, m), 7.19 (1H, t, J =7.8 Hz), 6.87-6.84 (2H, m), 4.05-3.59 (7H, m), 2.06 (3H, s), 1.32 (3H,t, J = 7.1 Hz), 1.25 (3H, t, J = 7.1 Hz). R.T. 1.20 min, m/z 374 (M + 1)89

¹H-NMR (CDCl₃) δ: 8.10-8.05 (2H, m), 7.85-7.79 (2H, m), 7.63-7.55 (2H,m), 7.35 (1H, d, J = 7.3 Hz), 3.55 (3H, s), 3.33 (3H, s), 2.60 (3H, s),2.27 (3H, s). R.T. 0.97 min, m/z 358 (M + 1) 90

¹H-NMR (CDCl₃) δ: 8.12-8.05 (2H, m), 7.62-7.54 (2H, m), 7.05-7.00 (2H,m), 6.88-6.84 (1H, m), 3.78 (3H, s), 3.56 (3H, s), 3.38 (3H, s). R.T.0.99 min, m/z 350 (M + 1) 91

¹H-NMR (CDCl₃) δ: 8.14-8.08 (2H, m), 7.63-7.55 (2H, m), 7.07-7.02 (2H,m), 6.90-6.85 (1H, m), 3.98 (2H, q, J = 7.1 Hz), 3.83-3.76 (5H, m), 1.36(3H, t, J = 7.1 Hz), 1.33 (3H, t, J = 7.1 Hz). R.T. 1.20 min, m/z 378(M + 1) 92

¹H-NMR (CDCl₃) δ: 8.14-8.07 (2H, m), 7.64-7.56 (2H, m), 7.14-7.10 (1H,m), 7.06-6.97 (2H, m), 3.91 (3H, s), 3.57 (3H, s), 3.39 (3H, s). R.T.0.97 min, m/z 350 (M + 1) 93

¹H-NMR (CDCl₃) δ: 8.14-8.08 (2H, m), 7.63-7.55 (2H, m), 7.14-7.10 (1H,m), 7.06-6.96 (2H, m), 3.97(2H, q, J = 7.1 Hz), 3.91 (3H, s), 3.78 (2H,q, J = 7.1 Hz), 1.35 (3H, t, J = 7.1 Hz), 1.31 (3H, t, J = 7.1 Hz). R.T.1.17 min, m/z 378 (M + 1) 94

¹H-NMR (CDCl₃) δ: 8.11-8.06 (2H, m), 7.62-7.54 (2H, m), 7.29-7.25 (1H,m), 6.97-6.94 (2H, m), 3.91 (3H, s), 3.54 (3H, s), 3.33 (3H, s). R.T.0.98 min, m/z 367 (M + 1) 95

¹H-NMR (CDCl₃) δ: 8.11-8.07 (2H, m), 7.61-7.53 (2H, m), 7.29-7.25 (1H,m), 6.97-6.93 (2H, m), 4.04-3.65 (7H, m), 1.33 (3H, t, J = 7.3 Hz), 1.26(3H, t, J = 7.3 Hz). R.T. 1.18 min, m/z 395 (M + 1) 96

¹H-NMR (CDCl₃) δ: 8.12-8.08 (2H, m), 7.63-7.55 (2H, m), 7.33 (1H, d, J =8.7 Hz), 6.91 (1H, d, J = 3.2 Hz), 6.85 (1H, dd, J = 8.7, 3.2 Hz),4.04-3.78 (7H, m), 1.34 (3H, t, J = 7.3 Hz), 1.29 (3H, t, J = 7.3 Hz).R.T. 1.23 min, m/z 395 (M + 1)

The points of the arrows represent the position of bonding with the mainskeleton.

Test Example 1 Cell Viability Evaluation Test using Human DermalFibroblasts Derived from a Friedreich Ataxia Patient

Compounds described herein were tested for their ability to rescueFriedreich ataxia patient-derived dermal fibroblasts stressed by theaddition of L-buthionine-(S,R)-sulfoximine (BSO).

A MEMα medium and a Medium 199 medium were obtained from ThermoScientific, and fetal bovine serum was obtained from DS Pharma. Basicfibroblast growth factor (b-FGF) was purchased from Funakoshi Co., Ltd.and epidermal growth factor (EGF) was purchased from PeproTech Inc.L-Buthionine-(S,R)-sulfoximine and bovine pancreas-derived insulin werepurchased from Sigma. Calcein-AM was purchased from DOJINDO. An assaymedium is a medium of 64% MEMα medium and 25% Medium 199 medium, andcontains 10% fetal bovine serum, EGF whose final concentration is 10ng/ml, 10 ng/ml of bFGF, and 10 μg/mL insulin. Cells were purchased fromCoriell Institute.

A test compound was dissolved in DMSO to make a 1 mM or 10 mM stocksolution. From this stock solution, serially diluted solutions werefurther prepared using DMSO and used in an assay.

Friedreich ataxia patient-derived human dermal fibroblasts weresuspended in an assay medium, seeded into a 384-well plate at 650cells/well/20 μl, and incubated at 37° C. in a 5% carbon dioxideincubator overnight. A test compound solution prepared in an assaymedium from the serially diluted solution (DMSO) at 5 times higher thanthe final concentration was added in 10 μL per well of the cell-seededplate. Then, 10 μL of 150 μM BSO solution was added. The amount of areaction solution was adjusted to be finally 50 μL, and the final BSOconcentration was made at 30 μM. The plate was incubated at 37° C. in 5%CO₂ for 48 hours, and then media were removed from all wells, and 20 μlof a Calcein-AM solution, which had been 550-fold diluted by PBS, wasadded to each well. The plate was incubated at 37° C. for 20 to 30minutes, and then fluorescence (485 nm/525 nm of excitation/radiationwavelength) was measured by a fluorescence plate reader.

The degree of the viability of fibroblasts that were not treated withBSO was regarded as 100%, the degree of the viability of cells that weretreated with BSO only (without a compound) was regarded as 0%, and theviability of cells that were treated with a compound was calculated.Results are shown in Table 6.

TABLE 6 Example EC₅₀ (nmol/L) 1 20-100 2 17 3 <20 4 3.7 5 14 6 <20 7 3 810 9 2 10 5.1 11 6.4 12 6.4 13 5.4 14 41 15 6 16 9.1 17 8.5 18 10.5 19 320 <3 21 7.9 22 1.9 23 5.9 24 2.4 25 21 26 7.2 27 4 28 4.8 29 12 30 1031 15 32 6 33 16 34 7 35 2.5 36 9.5 37 <3 38 18.8 39 6.1 40 11.6 41 12.942 5.1 43 20.1 44 17 45 8.4 46 14.9 47 4.9 48 4.1 49 4.3 50 16.8 51 11.852 19.1 53 11.4 54 12.1 55 21.1 56 14.5 57 18 58 0.9 59 4 60 17.4 61 4.262 5.5 63 18.4 64 47.7 65 9 66 6.7 67 >100 68 40.5 69 14.2 70 6.7 71 1572 20-100 73 7.2 74 <3 75 12.1 76 20.3 77 17 78 >100 79 39.1 80 10 8114.8 82 16.5 83 18.3 84 25.1 85 22.9 86 14.9 87 17.1 88 17.1 89 14.3 9014.0 91 19.0 92 30.2 93 29.1 94 22.6 95 34.3 96 18.9

As shown in Table 6, the compounds of the present disclosure exhibitedactivity to rescue Friedreich ataxia patient-derived fibroblastsstressed by addition of BSO in the cell viability evaluation test usinghuman dermal fibroblasts derived from Friedreich ataxia patients. Itshould be noted that the description “20-100” in Table 6 indicates thatan EC₅₀ value is a value between 20 nmol/L and 100 nmol/L; thedescriptions “<20” and “<3” indicate that an EC₅₀ value is a lowerconcentration than 20 nmol/L and 3 nmol/L, respectively; the description“>100” indicates that an EC₅₀ value is a higher concentration than 100nmol/L; and specific numerical values are omitted.

Test Example 2 A Cell Viability Evaluation Test in No Stress-InducedCell Death Using Human Dermal Fibroblasts Derived from ALS Patient

A compound is evaluated by measuring the degree of rescue of NOstress-induced cell death caused by the addition of SIN-1 and the liketo an ALS patient-derived fibroblast (refer to T. Aguirre (1998) Annalsof Neurology, 43(4): 452-457).

Test Example 3 ALS Animal Model Test

A compound is evaluated by administering the compound to an ALS modelmouse that spontaneously develops an ALS-like symptom for apredetermined period and measuring motor functions and the like (referto Takeo Ishiyama (2004) Brain Research, 1019: 226-236).

As described above, compounds of this disclosure are illustrated bypreferable embodiments. However, it will be understood that the scope ofthe present disclosure should be interpreted only by the claims. It willbe understood that the contents of patents, patent applications, andliteratures cited in the present specification should be incorporated byreference in their entirety to the present specification as if theircontents were specifically described in the present specification.

INDUSTRIAL APPLICABILITY

As described above, the compounds of the present invention are useful asa therapeutic and/or prophylactic drug for cancer, amyotrophic lateralsclerosis, Creutzfeldt-Jakob disease, Machado-Joseph disease,spinocerebellar ataxia, Huntington disease, Parkinson disease,Friedreich ataxia (FRDA), Alzheimer disease, atherosclerosis, myocardialinfarction, cerebral infarction, aging-related disease, diabetes,alcoholic liver injury, chronic obstructive pulmonary disease, Leber'shereditary optic neuropathy (LHON), mitochondrial myopathy,encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), LeighSyndrome, Kearns-Sayre syndrome (KSS), and the like.

1. A method of treating and/or preventing a disease caused by oraggravated by oxidative stress or mitochondrial dysfunction, comprisingadministering to a patient in need of the treatment and/or prevention atherapeutically effective amount of a compound according to formula (1):

or a reduced form thereof, or a pharmaceutically acceptable saltthereof, wherein R¹ and R² are each independently (1) a hydrogen atom,(2) an optionally substituted C₁₋₆alkyl group, an optionally substitutedC₂₋₆alkenyl group, or an optionally substituted C₂₋₆alkynyl group, (3)an optionally substituted C₃₋₁₀alicyclic hydrocarbon group (wherein thegroup may contain one or more unsaturated bonds), (4) an optionallysubstituted, 3 to 8-membered heterocyclic group (wherein the group maycontain one or more unsaturated bonds, and a carbon atom on the ring ofthe group is bonded with the nitrogen atom to which R¹ and R² areattached), (5) an optionally substituted C₆₋₁₀aryl group, or (6) anoptionally substituted, 5 to 12-membered monocyclic or polycyclicheteroaryl group (with the proviso that in the group, a carbon atom onits ring is bonded with the nitrogen atom to which R¹ and R² areattached), or R¹ and R² may be taken together with the nitrogen atom towhich they are attached to form an optionally substituted, 3 to8-membered, nitrogen-containing heterocycle (wherein the heterocycle maycontain one or more unsaturated bonds), and R³ is (1) an optionallysubstituted C₆₋₁₀aryl group, or (2) an optionally substituted, 5 to12-membered monocyclic or polycyclic heteroaryl group (with the provisothat in the group, a carbon atom on its ring is bonded with the carbonatom to which R³ is attached); or administering a pharmaceuticalcomposition comprising the therapeutically effective amount of thecompound of formula (1) and a pharmaceutically acceptable carrier, to apatient in need of the treatment and/or prevention; wherein the diseasecaused by or aggravated by oxidative stress or mitochondrial dysfunctionis selected from the group consisting of: amyotrophic lateral sclerosis(ALS), Huntington disease, Parkinson disease, Friedreich ataxia (FRDA),Alzheimer disease, multiple system atrophy (MS), Creutzfeldt-Jakobdisease, Machado-Joseph disease, spinocerebellar ataxia,atherosclerosis, myocardial infarction, cerebral infarction, diabetes,alcoholic liver injury, non-alcoholic steatohepatitis (NASH), pulmonaryfibrosis, hearing loss, spinal muscular atrophy (SMA), chronicobstructive pulmonary disease, Leber's hereditary optic neuropathy(LHON), mitochondrial myopathy, encephalopathy, lactic acidosis, andstroke-like episodes (MELAS), Leigh Syndrome and Kearns-Sayre syndrome(KSS), chronic progressive external ophthalmoplegia (CPEO), myoclonicepilepsy with ragged-red fibers (Fukuhara disease, MERRF, myoclonicepilepsy, myoclonic epilepsy syndrome), Pearson's disease (pancytopenia,multiple organ dysfunction syndrome), senile cognition disorder, cancer,and aging-related disease. 2.-15. (canceled)
 16. The method according toclaim 1, wherein the compound or a reduced form thereof, or apharmaceutically acceptable salt thereof, is wherein R¹ and R² are eachindependently (1) a hydrogen atom, (2) a C₁₋₆alkyl group, an optionallysubstituted C₂₋₆alkenyl group, or an optionally substituted C₂₋₆alkynylgroup (wherein each group is optionally substituted with one to threesubstituents independently selected from the group consisting of ahalogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxylgroup), (3) a C₃₋₁₀alicyclic hydrocarbon group (wherein the group maycontain one or more unsaturated bonds and the group is optionallysubstituted with one to three substituents independently selected fromthe group consisting of a C₁₋₆alkyl group, a halogen atom, a C₁₋₆alkoxygroup, a C₃₋₆cycloalkyl group, and a hydroxyl group), (4) a 3 to8-membered heterocyclic group (wherein the group may contain one or moreunsaturated bonds and the group is optionally substituted with one tofour groups independently selected from the group consisting of (a) ahalogen atom, (b) a C₁₋₆alkyl group (wherein the group is optionallysubstituted with one to three halogen atoms), (c) a C₁₋₆alkoxy group(wherein the group is optionally substituted with one to three halogenatoms), and (d) an amino group (wherein the group is optionallysubstituted with one or two C₁₋₆alkyl groups), with the proviso that inthe 3 to 8-membered heterocyclic group, when saturated, a carbon atom onits ring is bonded with the nitrogen atom to which R¹ and R² areattached), (5) a C₆₋₁₀aryl group (wherein the group is optionallysubstituted with one to four groups independently selected from thegroup consisting of (a) a halogen atom, (b) a C₁₋₆alkyl group (whereinthe group is optionally substituted with one to three halogen atoms),(c) a C₁₋₆alkoxy group (wherein the group is optionally substituted withone to three halogen atoms), and (d) an amino group (wherein the groupis optionally substituted with one or two C₁₋₆alkyl groups)), or (6) a 5to 12-membered monocyclic or polycyclic heteroaryl group (wherein thegroup is optionally substituted with one to four groups independentlyselected from the group consisting of (a) a halogen atom, (b) aC₁₋₆alkyl group (wherein the group is optionally substituted with one tothree halogen atoms), (c) a C₁₋₆alkoxy group (wherein the group isoptionally substituted with one to three halogen atoms), and (d) anamino group (wherein the group is optionally substituted with one or twoC₁₋₆alkyl groups), with the proviso that in the 5 to 12-memberedmonocyclic or polycyclic heteroaryl group, a carbon atom on its ring isbonded with the nitrogen atom to which R¹ and R² are attached), or R¹and R² may be taken together with the nitrogen atom to which they areattached to form a 3 to 8-membered, nitrogen-containing heterocycle(wherein the heterocycle may contain one or more unsaturated bonds andthe heterocycle is optionally substituted with one or two groupsindependently selected from the group consisting of a halogen atom, aC₁₋₆alkyl group, a C₁₋₆alkoxy group, and a hydroxyl group); R³ is (1) aC₆₋₁₀aryl group (wherein the group is optionally substituted with one toseven substituents independently selected from the group consisting of(a) a halogen atom, (b) a hydroxyl group, (c) a cyano group, (d) aC₁₋₆alkylsulfonyl group (wherein the C₁₋₆alkyl group is optionallysubstituted with one to three substituents independently selected fromthe group consisting of a halogen atom, a C₁₋₆alkoxy group, aC₃₋₆cycloalkyl group, and a hydroxyl group), (e) aC₁₋₆alkylaminosulfonyl group (wherein each C₁₋₆alkyl group is optionallysubstituted with one to three substituents independently selected fromthe group consisting of a halogen atom, a C₁₋₆alkoxy group, aC₃₋₆cycloalkyl group, and a hydroxyl group), (f) a C₁₋₆alkylcarbonylgroup (wherein the C₁₋₆alkyl group is optionally substituted with one tothree substituents independently selected from the group consisting of ahalogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxylgroup), (g) a C₁₋₆alkyl group (wherein the group is optionallysubstituted with one to three substituents independently selected fromthe group consisting of a halogen atom, a C₁₋₆alkoxy group, aC₃₋₆cycloalkyl group, and a hydroxyl group), (h) a C₁₋₆alkoxy group(wherein the group is optionally substituted with one to threesubstituents independently selected from the group consisting of ahalogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxylgroup), (i) a C₃₋₁₀cycloalkoxy group (wherein the group is optionallysubstituted with one to three substituents independently selected fromthe group consisting of a halogen atom, a C₁₋₆alkoxy group, aC₃₋₆cycloalkyl group, and a hydroxyl group), (j) —N(R⁴)COR⁵, (k)—CONR⁶R⁷, (l) —S(O)₂NR⁸R⁹, (m) an amino group (wherein the group isoptionally substituted with one or two C₁₋₆alkyl groups), and (n) a 4 to7-membered cyclic amino group (wherein the group is optionallysubstituted with one or two C₁₋₆alkyl groups), or two or moresubstituents on the C₆₋₁₀aryl group may be joined to form a 5 to8-membered non-aromatic carbocyclic or heterocyclic ring (wherein the 9to 16-membered ring, which is formed when the C₆₋₁₀aryl group is joinedwith the 5 to 8-membered non-aromatic carbocylic or heterocyclic ring,is optionally substituted with one or two C₁₋₆alkyl groups)), or (2) a 5to 12-membered monocyclic or polycyclic heteroaryl group (wherein thegroup is optionally substituted with one to nine substituentsindependently selected from the group consisting of (a) a halogen atom,(b) a hydroxyl group, (c) a cyano group, (d) a C₁₋₆alkylsulfonyl group(wherein the C₁₋₆alkyl group is optionally substituted with one to threesubstituents independently selected from the group consisting of ahalogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxylgroup), (e) a C₁₋₆alkylaminosulfonyl group (wherein each C₁₋₆alkyl groupis optionally substituted with one to three substituents independentlyselected from the group consisting of a halogen atom, a C₁₋₆alkoxygroup, a C₃₋₆cycloalkyl group, and a hydroxyl group), (f) aC₁₋₆alkylcarbonyl group (wherein the C₁₋₆alkyl group is optionallysubstituted with one to three substituents independently selected fromthe group consisting of a halogen atom, a C₁₋₆alkoxy group, aC₃₋₆cycloalkyl group, and a hydroxyl group), (g) a C₁₋₆alkyl group(wherein the group is optionally substituted with one to threesubstituents independently selected from the group consisting of ahalogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxylgroup), (h) a C₁₋₆alkoxy group (wherein the group is optionallysubstituted with one to three substituents independently selected fromthe group consisting of a halogen atom, a C₁₋₆alkoxy group, aC₃₋₆cycloalkyl group, and a hydroxyl group), (i) a C₃₋₁₀cycloalkoxygroup (wherein the group is optionally substituted with one to threesubstituents independently selected from the group consisting of ahalogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxylgroup), (j) a C₆₋₁₀aryl group (wherein the group is optionallysubstituted with one to three substituents independently selected fromthe group consisting of a halogen atom, a C₁₋₆alkoxy group, aC₃₋₆cycloalkyl group, and a hydroxyl group), (k) —N(R¹⁰)COR¹¹, (l)—CONR¹²R¹³, (m) an amino group (wherein the group is optionallysubstituted with one or two C₁₋₆alkyl groups), and (n) a 4 to 7-memberedcyclic amino group (wherein the group is optionally substituted with oneor two C₁₋₆alkyl groups), or two or more substituents on the 5 to12-membered monocyclic or polycyclic heteroaryl group may be joined toform a 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring(wherein the 8 to 18-membered ring, which is formed when the 5 to12-membered monocyclic or polycyclic heteroaryl group is joined with the5 to 8-membered non-aromatic carbocylic or heterocyclic ring, isoptionally substituted with one or two C₁₋₆alkyl groups), with theproviso that in the 5 to 12-membered monocyclic or polycyclic heteroarylgroup, a carbon atom on its ring is bonded with the carbon atom to whichR³ is attached); and R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹², and R¹³ are eachindependently a hydrogen atom or a C₁₋₁₀alkyl group optionallysubstituted with one to five fluorine atoms, or R⁶ and R⁷, R⁸ and R⁹ ,and R¹² and R¹³ each independently may be taken together to form a 4 to10-membered, nitrogen-containing heterocycle.
 17. The method accordingto claim 16, wherein the compound or a reduced form thereof, or apharmaceutically acceptable salt thereof, is wherein R³ is (1) aC₆₋₁₀aryl group (wherein the group is optionally substituted with one toseven substituents independently selected from the group consisting of(a) a halogen atom, (b) a cyano group, (c) a C₁₋₆alkyl group (whereinthe group is optionally substituted with one to three substituentsindependently selected from the group consisting of a halogen atom, aC₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxyl group), (d) aC₁₋₆alkoxy group (wherein the C₁₋₆alkyl group is optionally substitutedwith one to three substituents independently selected from the groupconsisting of a halogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkylgroup, and a hydroxyl group), (e) a C₃₋₁₀cycloalkoxy group (wherein thegroup is optionally substituted with one to three substituentsindependently selected from the group consisting of a halogen atom, aC₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxyl group), (f)—N(R⁴)COR⁵, (g) —CONR⁶R⁷, (h) —S(O)₂NR⁸R⁹, (i) an amino group (whereinthe group is optionally substituted with one or two C₁₋₆alkyl groups),and (j) a 4 to 7-membered cyclic amino group (wherein the group isoptionally substituted with one or two C₁₋₆alkyl groups), or twosubstituents on the C₆₋₁₀aryl group may be joined to form a 5 to8-membered non-aromatic carbocyclic or heterocyclic ring (wherein the 9to 16-membered ring, which is formed when the C₆₋₁₀aryl group is joinedwith the 5 to 8-membered non-aromatic carbocylic or heterocyclic ring,is optionally substituted with one or two C₁₋₆alkyl groups; or in someembodiments, the 5 to 8-membered non-aromatic carbocyclic orheterocyclic ring is optionally substituted with one or two C₁₋₆alkylgroups)), or (2) a 5 to 12-membered monocyclic or polycyclic heteroarylgroup (wherein the group is optionally substituted with one to ninesubstituents independently selected from the group consisting of (a) aC₁₋₆alkyl group (wherein the group is optionally substituted with one tothree substituents independently selected from the group consisting of ahalogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxylgroup), (b) a C₁₋₆alkoxy group (wherein the group is optionallysubstituted with one to three substituents independently selected fromthe group consisting of a halogen atom, a C₁₋₆alkoxy group, aC₃₋₆cycloalkyl group, and a hydroxyl group), (c) a C₃₋₁₀cycloalkoxygroup (wherein the group is optionally substituted with one to threesubstituents independently selected from the group consisting of ahalogen atom, a C₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxylgroup), (d) a C₆₋₁₀aryl group (wherein the group is optionallysubstituted with one to three substituents independently selected fromthe group consisting of a halogen atom, a C₁₋₆alkoxy group, aC₃₋₆cycloalkyl group, and a hydroxyl group), (e) —N(R¹⁰)COR¹¹, (f)—CONR¹²R¹³, (g) an amino group (wherein the group is optionallysubstituted with one or two C₁₋₆alkyl groups), and (h) a 4 to 7-memberedcyclic amino group (wherein the group is optionally substituted with oneor two C₁₋₆alkyl groups), or two substituents on the 5 to 12-memberedmonocyclic or polycyclic heteroaryl group may be joined to form a 5 to8-membered non-aromatic carbocyclic or heterocyclic ring (wherein the 8to 18-membered ring, which is formed when the 5 to 12-memberedmonocyclic or polycyclic heteroaryl group is joined with the 5 to8-membered non-aromatic carbocylic or heterocyclic ring, is optionallysubstituted with one or two C₁₋₆alkyl groups; or in some embodiments,the 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring isoptionally substituted with one or two C₁₋₆alkyl groups), with theproviso that in the 5 to 12-membered monocyclic or polycyclic heteroarylgroup, a carbon atom on its ring is bonded with the carbon atom to whichR³ is attached); and R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, and R¹³ are eachindependently a hydrogen atom or a C₁₋₁₀alkyl group optionallysubstituted with one to five fluorine atoms, or R⁶ and R⁷, R⁸ and R⁹ ,and R¹² and R¹³ each independently may be taken together to form a 4 to10-membered, nitrogen-containing heterocycle.
 18. The method accordingto claim 16, wherein the compound or a reduced form thereof, or apharmaceutically acceptable salt thereof, is wherein R³ is (1) aC₆₋₁₀aryl group (wherein the group is optionally substituted with one toseven substituents independently selected from the group consisting of(a) a halogen atom, (b) a cyano group, (c) a C₁₋₆alkyl group (whereinthe group is optionally substituted with one to three substituentsindependently selected from the group consisting of a halogen atom and aC₁₋₆alkoxy group), (d) a C₁₋₆alkoxy group (wherein the C₁₋₆alkyl groupis optionally substituted with one to three halogen atoms), (e)—N(R⁴)COR⁵, (f) —CONR⁶R⁷, (g) —S(O)₂NR⁸R⁹, (h) an amino group (whereinthe group is optionally substituted with one or two C₁₋₆alkyl groups),and (i) a 4 to 7-membered cyclic amino group (wherein the group isoptionally substituted with one or two C₁₋₆alkyl groups), or twosubstituents on the C₆₋₁₀aryl group may be joined to form a 5 to8-membered non-aromatic heterocycle (wherein the 5 to 8-memberednon-aromatic heterocycle is optionally substituted with one or twoC₁₋₆alkyl groups)), or (2) a 5 to 12-membered monocyclic or polycyclicheteroaryl group (wherein the group is optionally substituted with oneto nine substituents independently selected from the group consisting of(a) a C₁₋₆alkyl group, (b) a C₁₋₆alkoxy group, (c) a C₃₋₁₀cycloalkoxygroup, (d) a C₆₋₁₀aryl group, (e) —N(R¹⁰)COR¹¹, (f) R¹³, (g) an aminogroup (wherein the group is optionally substituted with one or twoC₁₋₆alkyl groups), and (h) a 4 to 7-membered cyclic amino group (whereinthe group is optionally substituted with one or two C₁₋₆alkyl groups),or two substituents on the 5 to 12-membered monocyclic or polycyclicheteroaryl group may be joined to form a 5 to 8-membered non-aromaticheterocycle (wherein the 5 to 8-membered non-aromatic heterocycle isoptionally substituted with one or two C₁₋₆alkyl groups), with theproviso that in the 5 to 12-membered monocyclic or polycyclic heteroarylgroup, a carbon atom on its ring is bonded with the carbon atom to whichR³ is attached); and R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², and R¹³ areeach independently a hydrogen atom or a C₁₋₁₀alkyl group, or R⁶ and R⁷,R⁸ and R⁹, and R¹² and R¹³ each independently may be taken together toform a 4 to 10-membered, nitrogen-containing heterocycle.
 19. The methodaccording to claim 16, wherein the compound or a reduced form thereof,or a pharmaceutically acceptable salt thereof, is wherein R¹ and R² areeach independently (1) a hydrogen atom, (2) a C₁₋₆alkyl group (whereinthe group is optionally substituted with one to three substituentsindependently selected from the group consisting of a halogen atom, aC₁₋₆alkoxy group, a C₃₋₆cycloalkyl group, and a hydroxyl group), or (3)a C₃₋₁₀alicyclic hydrocarbon group (wherein the group may contain one ormore unsaturated bonds and the group is optionally substituted with oneto three substituents independently selected from the group consistingof a halogen atom, a C₁₋₆alkyl group, a C₁₋₆alkoxy group, aC₃₋₆cycloalkyl group, and a hydroxyl group), or R¹ and R² are takentogether with the nitrogen atom to which they are attached to form a 3to 8-membered, nitrogen-containing heterocycle (wherein the heterocyclemay contain one or more unsaturated bonds and the heterocycle isoptionally substituted with one or two groups independently selectedfrom the group consisting of a halogen atom, a C₁₋₆alkyl group, aC₁₋₆alkoxy group, and a hydroxyl group).
 20. The method according toclaim 16, wherein the compound or a reduced form thereof, or apharmaceutically acceptable salt thereof, is wherein R¹ and R² are eachindependently a hydrogen atom, or a C₁₋₆alkyl group (wherein the groupis optionally substituted with one to three C₁₋₆alkoxy groups), or R¹and R² are taken together with the nitrogen atom to which they areattached to form a 3 to 8-membered, nitrogen-containing heterocycle(wherein the heterocycle may contain one or more unsaturated bonds andthe heterocycle is optionally substituted with one or two groupsindependently selected from the group consisting of a C₁₋₆alkyl group, aC₁₋₆alkoxy group, and a hydroxyl group).
 21. The method according toclaim 16, wherein the compound or a reduced form thereof, or apharmaceutically acceptable salt thereof, is wherein R¹ and R² are eachindependently an optionally substituted C₁₋₆alkyl group, or R¹ and R²may be taken together with the nitrogen atom to which they are attachedto form an optionally substituted, 3 to 8-membered, nitrogen-containingheterocycle (the heterocycle may contain one or more unsaturated bonds),and R³ is an optionally substituted C₆₋₁₀aryl group, or an optionallysubstituted, 5 to 12-membered monocyclic or polycyclic heteroaryl group(with the proviso that in the group, a carbon atom on its ring is bondedwith the carbon atom to which R³ is attached).
 22. The method accordingto claim 16, wherein the compound or a reduced form thereof, or apharmaceutically acceptable salt thereof, is wherein R¹ and R² are eachindependently a C₁₋₆alkyl group (wherein the group is optionallysubstituted with one C₁₋₆alkoxy group), or R¹ and R² may be takentogether with the nitrogen atom to which they are attached to form a 3to 8-membered, nitrogen-containing heterocycle (wherein the heterocyclemay contain one or more unsaturated bonds and the heterocycle isoptionally substituted with one C₁₋₆alkyl group); R³ is (1) a C₆₋₁₀arylgroup (wherein the group is optionally substituted with one to sevensubstituents independently selected from the group consisting of (a)halogen atom, (b) cyano group, (c) a C₁₋₆alkyl group (wherein the groupis optionally substituted with one to three substituents independentlyselected from the group consisting of a halogen atom and a C₁₋₆alkoxygroup), (d) a C₁₋₆alkoxy group (wherein the C₁₋₆alkyl group isoptionally substituted with one to three halogen atoms), (e) —N(R⁴)COR⁵,(f) —CONR⁶R⁷, (g) —S(O)₂NR⁸R⁹, (h) an amino group (wherein the group isoptionally substituted with one or two C₁₋₆alkyl groups), and (i) a 4 to7-membered cyclic amino group (wherein the group is optionallysubstituted with one or two C₁₋₆alkyl groups), or two substituents onthe C₆₋₁₀aryl group may be joined to form a 5 to 8-membered non-aromaticcarbocyclic or heterocyclic ring (wherein the 9 to 16-membered ring,which is formed when the C₆₋₁₀aryl group is joined with the 5 to8-membered non-aromatic carbocylic or heterocyclic ring, is optionallysubstituted with one or two C₁₋₆alkyl groups; or in some embodiments,the 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring isoptionally substituted with one or two C₁₋₆alkyl groups)), with theproviso that in the 5 to 12-membered monocyclic or polycyclic heteroarylgroup, a carbon atom on its ring is bonded with the carbon atom to whichR³ is attached), or (2) a 5 to 12-membered monocyclic or polycyclicheteroaryl group (wherein the group is optionally substituted with oneto nine substituents independently selected from the group consisting of(a) a C₁₋₆alkyl group, (b) a C₁₋₆alkoxy group, (c) a C₆₋₁₀aryl group,and (d) a 4 to 7-membered cyclic amino group (wherein the group isoptionally substituted with one or two C₁₋₆alkyl groups), with theproviso that in the 5 to 12-membered monocyclic or polycyclic heteroarylgroup, a carbon atom on its ring is bonded with the carbon atom to whichR³ is attached); and R⁴, R⁵, R⁶, and R⁷ are each independently ahydrogen atom or a C₁₋₁₀alkyl group, and R⁸ and R⁹ may be taken togetherto form a 4 to 10-membered, nitrogen-containing heterocycle (wherein theheterocycle may contain one or more unsaturated bonds).
 23. The methodaccording to claim 16, wherein the compound or a reduced form thereof,or a pharmaceutically acceptable salt thereof, is wherein R¹ and R² areeach independently a C₁₋₆alkyl group (wherein the group is optionallysubstituted with one C₁₋₆alkoxy group).
 24. The method according toclaim 16, wherein the compound or a reduced form thereof, or apharmaceutically acceptable salt thereof, is wherein R¹ and R² takentogether with the nitrogen atom to which they are attached to form a 3to 8-membered, nitrogen-containing heterocycle (wherein the heterocyclemay contain one or more unsaturated bonds and the heterocycle isoptionally substituted with one C₁₋₆alkyl group).
 25. The methodaccording to claim 16, wherein the compound or a reduced form thereof,or a pharmaceutically acceptable salt thereof, is wherein R³ is aC₆₋₁₀aryl group (wherein the group is optionally substituted with one toseven substituents independently selected from the group consisting of(a) halogen atom, (b) cyano group, (c) a C₁₋₆alkyl group (wherein thegroup is optionally substituted with one to three substituentsindependently selected from the group consisting of a halogen atom and aC₁₋₆alkoxy group), (d) a C₁₋₆alkoxy group (wherein the C₁₋₆alkyl groupis optionally substituted with one to three halogen atoms), (e)—N(R⁴)COR⁵, (f) —CONR⁶R⁷, (g) —S(O)₂NR⁸R⁹, (h) an amino group (whereinthe group is optionally substituted with one or two C₁₋₆alkyl groups),and (i) a 4 to 7-membered cyclic amino group (wherein the group isoptionally substituted with one or two C₁₋₆alkyl groups), or twosubstituents on the C₆₋₁₀aryl group may be joined to form a 5 to8-membered non-aromatic carbocyclic or heterocyclic ring (wherein the 9to 16-membered ring, which is formed when the C₆₋₁₀aryl group is joinedwith the 5 to 8-membered non-aromatic carbocylic or heterocyclic ring,is optionally substituted with one or two C₁₋₆alkyl groups; or in someembodiments, the 5 to 8-membered non-aromatic carbocyclic orheterocyclic ring is optionally substituted with one or two C₁₋₆alkylgroups)); and R⁴, R⁵, R⁶, and R⁷ are each independently a hydrogen atomor a C₁₋₁₀alkyl group, and R⁸ and R⁹ may be taken together to form a 4to 10-membered, nitrogen-containing heterocycle (wherein the heterocyclemay contain one or more unsaturated bonds).
 26. The method according toclaim 16, wherein the compound or a reduced form thereof, or apharmaceutically acceptable salt thereof, is wherein R³ is a 5 to12-membered monocyclic or polycyclic heteroaryl group (wherein the groupis optionally substituted with one to nine substituents independentlyselected from the group consisting of (a) a C₁₋₆alkyl group, (b) aC₁₋₆alkoxy group, (c) a C₆₋₁₀aryl group, and (d) a 4 to 7-memberedcyclic amino group (wherein the group is optionally substituted with oneor two C₁₋₆alkyl groups), with the proviso that in the 5 to 12-memberedmonocyclic or polycyclic heteroaryl group, a carbon atom on its ring isbonded with the carbon atom to which R³ is attached).
 27. The methodaccording to claim 16, wherein the compound or a reduced form thereof,or a pharmaceutically acceptable salt thereof, is wherein the compoundis selected from the group consisting of the following compounds:


28. The method according to claim 16, wherein the compound or a reducedform thereof, or a pharmaceutically acceptable salt thereof, is whereinthe compound is selected from the group consisting of the followingcompounds:2-(dimethylamino)-4-(4-methylphenyl)-5H-naphth[1,2-d]imidazol-5-one;2-(dimethylamino)-4-(2-methylphenyl)-5H-naphth[1,2-d]imidazol-5-one;4-(2-methylphenyl)-2-(4-methylpiperazin-1-yl)-5H-naphth[1,2-d]imidazol-5-one;2-(dimethylamino)-4-[2-(morpholin-4-yl)phenyl]-5H-naphth[1,2-d]imidazol-5-one;2-(dimethylamino)-4-[2-(trifluoromethyl)phenyl]-5H-naphth[1,2-d]imidazol-5-one;2-(dimethylamino)-4-[2-methyl-4-(trifluoromethyl)phenyl]-5H-naphth[1,2-d]imidazol-5-one;2-(diethylamino)-4-(2-methylphenyl)-5H-naphth[1,2-d]imidazol-5-one;2-(dimethylamino)-4-[2-methyl-4-(trifluoromethoxy)phenyl]-5H-naphth[1,2-d]imidazol-5-one;4-(2-chlorophenyl)-2-(dimethylamino)-5H-naphth[1,2-d]imidazol-5-one;2-(dimethylamino)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-5H-naphth[1,2-d]imidazol-5-one;2-[(2-dimethylamino)-5-oxo-5H-naphth[1,2-d]imidazol-4-yl]benzonitrile;4-[(2-dimethylamino)-5-oxo-5H-naphth[1,2-d]imidazol-4-yl]-3-methylbenzonitrile;and2-(dimethylamino)-4-(2-chloro-4-methoxyphenyl)-5H-naphth[1,2-d]imidazol-5-one.29. The method of claim 16, wherein the compound is selected from thegroup consisting of:


30. The method of claim 16, wherein the compound is


31. The method of claim 16, wherein the compound is


32. The method of claim 16, wherein the compound is